Journal für Hirnforschung: Band 19, Heft 3 1978 [Reprint 2021 ed.] 9783112519721, 9783112519714

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ISSN 0021 - 8359

Heft 3 • 1978 • Band 19

J O U I ^ H S !

für Hirnforschung Internationales Journal für Neurobiologie Begründet von Cécile und Oskar Vogt Herausgeber: J. Anthony, Paris • A. Hopf, Düsseldorf W. Kirsche, Berlin • J.Szentägothai, Budapest Schriftleitung: W. Kirsche, Berlin Wiss. Sekretär: J.Wenzel, Berlin

Akademie-Verlag • Berlin EVP25.-M-32105

ISSN 0021 - 8359

Journal

J . Hirnforsch. 19 (1978) 1 8 9 - 1 9 1

•

Internationales Journal für Neurobiologie

n

f Q p

Hirnforschung

H e f t 3 • 1978 • B a n d 19

V.

Janos Szentägothai zur Vollendung des 65. Lebensjahres Verehrter Jubilar, lieber Herr

SZENTÄGOTHAI !

Zwar etwas verspätet, aber deshalb nicht minder herzlich gedenken Herausgeber und Mitherausgeber des Journals für Hirnforschung der Vollendung Ihres 65. Lebensjahres. Unsere Glückwünsche verbinden wir mit dem Dank für Ihre Mitwirkung als Herausgeber und Redakteur unseres Journals seit nunmehr 16 Jahren. Ferner ziert Ihr Name seit 20 Jahren auch die Titelseite der Bände der Zeitschrift für mikroskopisch-anatomische Forschung, in der Sie vor H i r n f o r s c h u n g , Bd. 19, H r f t 3

43 Jahren Ihre erste wissenschaftliche Arbeit mit einem neurohistologischen Thema veröffentlicht haben. Wenn diese Glückwunschadresse nicht zum eigentlichen Termin Ihres Geburtstages am 31. Oktober 1977 erscheint, sondern erst im Jahre 1978, dann ergibt sich für uns die Möglichkeit, eines weiteren Ihre wissenschaftliche Arbeit betreffenden Jubiläums zu gedenken. Vor 40 Jahren erschienen im Ergänzungsheft zum 85. Band des Anatomischen Anzeigers die Verhandlungen der 45. Versammlung der Anato14

190

W. Kirsche

mischen Gesellschaft mit mehreren Ihr Forschungsgebiet betreffenden Vorträgen. Im gleichen J a h r veröffentlichten Sie in der Zeitschrift für mikroskopischanatomische Forschung Ihre grundlegende Arbeit über „Die »Syncytielle Natur« des vegetativen Nervensystems." Diese auf Ergebnissen Ihrer Untersuchungen beruhende überzeugende Verteidigung der Neuronentheorie war in damaliger Zeit eine besondere Leistung, weil man ein J a h r vorher zu der 45. Versammlung der Anatomischen Gesellschaft die Neuronentheorie „zu Grabe getragen" hatte, und da in der deutschsprachigen Literatur diese Theorie allgemein abgelehnt wurde. Die weitere Entwicklung unserer Wissenschaft hat bekanntlich später gezeigt, daß der von Ihnen eingeschlagene Weg zwar von mancher Seite erheblichen Widerspruch zum Teil auch in sehr unsachlicher Form hervorrief, andererseits jedoch zur Aufdeckung der Wahrheit führte. Bereits als Student haben Sie bei M. v. L E N H O S S E K im Anatomischen Institut in Budapest gearbeitet und seitdem sich mit Liebe und Leidenschaft der Erforschung des Nervensystems gewidmet. Ihre zahlreichen wissenschaftlichen Arbeiten, Ihre Handbuchbeiträge und Monographien sowie auch die zahlreichen Arbeiten Ihrer Schüler befassen sich mit Fragen einer funktionsbezogenen Morphologie des Nervensystems. Das von Ihnen vor 40 Jahren vertretene Konzept der Neuronentheorie haben Sie bis zu Ihren jüngsten Arbeiten nicht nur verteidigt, sondern durch zahlreiche neue Erkenntnisse weiter entwickelt. Grundlegende Befunde beziehen sich auf die Koordination von licht- und elektronenmikrcskopischen sowie histochemischen Befunden am Ganglion ciliare, auf experimentelle Arbeiten zur funktionellen Morphologie des vestibulo-oculären Systems, auf die Synaptologie verschiedener Grisea im Rückenmark und Hirnstamm und auf die anatomischen Grundlagen der Erregung und Hemmung in verschiedenen Gebieten des Zentralnervensystems. Durch Kombination der GoLGi-Methode mit elektronenmikroskopischen Untersuchungen auf der Grundlage verschiedener experimenteller Versuchsanordnungen gelang Ihnen die Aufdeckung entscheidender Grundlagen zur synaptischen Organisation im Kleinhirn. Die Berücksichtigung stereoskopischer Zusammenhänge erbrachte wesentliche Einsichten, welche in der gemeinsam mit J . C . E C C L E S und M. I T O verfaßten Monographie 'The cerebellum as a neuronal machine' ihren Niederschlag fanden. Ferner haben Ihre zahlreichen Arbeiten zur neuronalen Organisation der Hirnrinde neue Ergebnisse erbracht, wobei auch stereologische Vorstellungen ein neues Konzept über die Wirkungsfelder von Hemmungsneuronen ergaben. Ihre Untersuchungen über die synaptische Organisation der Hirnrinde, über Fragen der Plasti-

zität des Gehirns, über geometrische Aspekte der Neuropilorganisation stehen gegenwärtig im Mittelpunkt Ihres Interesses, wobei Sie stets bestrebt sind, die Morphologie als dynamische Wissenschaft zu sehen, die ohne Bezug zur Funktion nicht mehr vorstellbar ist. Diese Einstellung widerspiegeln sowohl Ihre wissenschaftlichen Veröffentlichungen in Zeitschriften als auch Ihre Monographien, die sich mit dem vestibulooculären System (1952) der "Hypothalamic control of the anterior pituitary" (1962), dem "Cerebellum as a neural machine" (1967) sowie mit "Conceptual models of neural Organization" (1975) befassen. Darüberhinaus zeigt Ihr Lehrbuch zur „Funktionellen Anatomie" (1975) eine moderne Einstellung zu unserem Fachgebiet, und der gemeinsam mit F . Kiss herausgegebene „Anatomische Atlas" erlebte bereits die 68. Auflage in zahlreichen Sprachen, davon 27 Auflagen in deutscher Sprache. Als Hochschullehrer haben Sie sich mit der ganzen Kraft Ihrer Persönlichkeit eingesetzt, humanistisch gesinnte Ärzte mit großen Kenntnissen auszubilden, die Ihr Wissen und Können diszipliniert und verantwortungsbewußt anwenden. Ihre Leistungen als einer der bedeutendsten international anerkannten Hirnforscher wurden durch zahlreiche Mitgliedschaften und Ehrenmitgliedschaften in Akademien und wissenschaftlichen Gesellschaften gewürdigt. So sind Sie unter anderem Ehrenmitglied der Akademie der Wissenschaften der UdSSR, auswärtiges Ehrenmitglied der "American Academy of Arts and Sciences", Boston, auswärtiges Mitglied der "National Academy of Sciences of the United States", Washington, Mitglied der „Deutschen Akademie der Naturforscher L E O P O L D I N A " und der „Académie Royale de Médicine de Belgique", Bruxelles. Ferner wurden Ihnen zahlreiche Auszeichnungen zuteil, darunter der Staatspreis I. Klasse, der Kossuth Preis I I . Klasse, die SemmelweisMedaille Ihres Landes und ferner die HufelandMedaille der D D R und der Karl Spencer Lashley Preis (USA). Seit 1948 sind Sie korrespondierendes Mitglied und seit 1967 ordentliches Mitglied der Ungarischen Akademie der Wissenschaften und als Zeichen der Anerkennung Ihrer wissenschaftlichen Leistungen und als Anerkennung Ihrer Persönlichkeit wurden Sie 1977 einstimmig zum Präsidenten Ihrer Akademie gewählt. Wir schätzen uns glücklich, daß Sie, verehrter lieber Herr Szentâgothai, trotz Ihrer vielseitigen Verpflichtungen seit vielen Jahren bis zum heutigen Tage an der Gestaltung unseres Journals mitgewirkt haben. Unseren Dank für Ihre Mitarbeit und für die dadurch zum Ausdruck kommende freundschaftliche Gesinnung verbinden wir mit dem Wunsch für gute

Jänos Szentagothai zur Vollendung des 65. Lebensjahres

Gesundheit und weitere so erfolgreiche Schaffenskraft für viele Jahre, die Ihnen wie bisher Freude bei der Aufdeckung neuer Erkenntnisse auf dem Gebiete der Hirnforschung und persönliches Wohlergehen bringen mögen. Rückblickend auf den Beginn Ihrer wissenschaftlichen Arbeit, als Sie nahezu auf einsamer Insel stehend für die Anerkennung der Neuronentheorie eintraten, können Sie heute — 40 Jahre später — mit Befriedigung feststellen, daß Ihre Arbeit Früchte

191

getragen hat, indem Sie in den einführenden Bemerkungen zu dem Symposium in Tihany (1976) "Neuron Concept Today" unter anderem zusammenfassend formulieren konnten: " I do not see any reason, for the time being, to modify or reject any of the fundamental assumptions upon which the neuron concept has been based". Auch dazu unseren herzlichsten Glückwunsch! W.

14*

KIRSCHE

J . Hirnforsch. 19 (1978) 193 - 201

1st Department of Anatomy, Semmelweis University Medical School, Budapest

Quantitative histological studies on the lateral geniculate nucleus in the cat. III. Distribution of different types of neurons in the several layers of LGN

M a g d a MADARASZ, J . G E R L E , F . H A J D U , G y . SOMOGYI a n d T e r 6 z TOMBOL

W i t h 6 figures (Received 7 t h J u l y 1977)

Summary: An a t t e m p t is made on the definition of proportional distribution of the different types of neurons in the layers of L G N by means of quantitative method. On the basis of nuclear volume, nuclear and cell diameters the different types of neurons were separated according to their size and shape. The ratio of relay and interneurons proved to be 2 : 1 in all layers of L G N of cat. The proportional distribution of further subgroups of neurons was also defined. The bilateral connections between the relay and interneurons based on initial axon collateral of T C R neurons and on axon terminals and dendritic appendages of INs, are also calculated. The interneurons — in the L G N — have widespread contacts with both types of relay neurons, similarly the relay neurons contact the interneurons. The numerical data of morphological observations are in accord with the results of physiologists.

Introduction For the identification of various types of neurons the Golgi stain is the most adequate (CAJAL 1 9 1 1 , FAMIGLIETTI a n d P E T E R S 1 9 7 2 , GROSSMANN e t al.

1973,

O'LEARY

1963,

1940,

LEONTOVICH

and

ZHUKOVA

MOREST 1 9 7 1 , SCHEIBEL a n d SCHEIBEL 1 9 6 6 , SHKOLNIK-YARROS

1 9 6 2 , SZENTAGOTHAI 4 9 6 3 ,

1972,

1973

and SZENTAGOTHAI et al. 1 9 6 6 ) . Two main neuron types have been identified in the LGN, so far: relay and Golgi type I I interneurons. Further subdivisions of neurons were made by several authors on the basis of additional criteria (CLELAND et al. 1 9 7 1 , GUILLERY

1966,

SZENTAGOTHAI

1973,

TOMBOL

1968,

1969 a, b). In the group of relay neurons two subgroups were distinguished, large and medium-size relay cells. The large relay neurons project both the primary and secondary visual cortex (GAREY and P O W E L L 1 9 6 7 ) . The medium-size or otherwise principal relay cells have connections only to the primary visual cortex. The interneurons were divided also into two subgroups on the basis of dendritic and mainly axonal characteristics (TOMBOL 1 9 6 9 ) . Golgi pictures show additionally some fusiform neurons which are arranged mostly in or at the laminar borders and belong to the interlaminar system of the LGN. The present study aims at defining, by quantitative methods, the different types of neurons and their proportional distributions in the several layers of the LGN. On the basis of nuclear volume and nuclear diameters it is often possible to separate various

types of neurons and also to determine their absolute and relative numbers more realistically than would be ever possible by means of the selective Golgi procedure. Materials and Methods The same section series (KLÜVER and BARRERA 1953) were used for this study as for counting the cell numbers and densities in the preceding paper (II part of this series). A direct comparison of the sizes of cells has been made in Nissl and Golgi stained material. F o r the separation of various cell types by the aid of karyometric dot diagrams (PALKOVITS and FISCHER 1968), the largest diameter and the perpendicular short diameter of the neuron nuclei were measured under projection with 3,000 x magnification. Elongation (excentricity) of nuclei was determined b5' the quotient of the longest and (perpendicular) short diameter. T h e volume of nuclei was also calculated (PALKOVITS and FISCHER 1968). The diameters of 300 — 400 nuclei were measured in each layer of L G N and in three different series. The diameters of about 1,000 cell nuclei were measured by total scanning of the entire surface of L G N . Two types of dot diagrams were prepared. In the first type the long diameters were plotted against log. volume, in the second type log. volumes were plotted against the excentricity ( = long/short diameter). Two main groups of cells could be distinguished by aid of the two ways of displaying the quant i t a t i v e data. I n addition the diameters of 500 cells were also measured and the result was represented on dot diagrams.

Results The measurements of cell body diameters yield similar data as found on Golgi specimens. The longest and the perpendicular short diameters of relay cells

194

Madaràsz, M., J . Gerle, F. Hajdu, Gy. Somogyi and T. Tòmbòl

LAYER

log. voi.

A

3.2 3.0 28 -

•

./

i

• V

2.624.-

^•-.ZC'-i's-»

22 -

!

20 1.6

1,8

H

h 22 24

20

26

2,8 30

3,2 3A 3,6 26

1 H 4,0 4,2 4.4 4.6 4,8

LAYER

log VOL

22

--

20

--

ld.

A,

23

26 24 v-

22

/

/

20 -1 f1,6 13

20

22

H 1 2,4 2 6

1 I28 30

22

-I

2A

C

I- -43,6 3 «

LAYER

log. voi.

i h 4.4 4.6 4,8 4 3

4,0 4.2

5,2 5A

ld

B

Ì 4 -3,2 - 3,0 - 23

--

2.6 24

2,2 2,0 -t- -i1.6 1.8 2 0

-t-

22

-t24

-t- H 2,6 2»

1

20

1

22

h 3,4 3,6

-t3,8 4,0 4,2 44

H t4,6 4.8 l.d.

Fig. 1 a, b, c. Dot diagrams of cell nuclei separately in the three main layers of LGN. The logarithm volume is dotted against the long diameter in mm (3,000 X magnification).

Quantitative histological studies on LGN

exc

LAYER

A,

1 3,0

1 3,1

1 2,2

1 1 3,3 log.vol.

LAYER

B

. 3fo

3I1

3'.2

log.vol.

195

22 20 1.8

1.6 1,4.

1,2 1-0 —I 20

1 2,1

1 2.2

I 23

1 24

1 2,5

1 26

1 2,7

1—i 2,8 2 9

exc.

22 2,0 1'8 - f . is

1,2 1,0

'

..

:

-i' V* ;•

"A-

Z0

-yy • . / v.«. *

-i " .

A : VV:: V • ••: • V ..'. •• • 21

..V _ _ o

i

•/•ivvV :•!• ••/• V ^ -

2.2

2I3

2¡4

2.5 2 £

2,7

2^

Fig. 2 a, b, c. Dot diagrams of cell nuclei separately in the three layers of LGN. The excentricity is dotted against the logarithm volume. The circumscribed areas are the subgroups of cell nuclei.

19G

Madaràsz, M., J . Gerle, F. Hajdu, Gy. Somogyi and T. ïdmbol

were 35 X 28 ¡xm (large relay) and 26 X 18 [im (principal cells); the diameters of Golgi II interneurons were 1 0 x 1 5 [Am (Golgi II a) and 1.5x18 (Am (Golgi l i b ) respectively. The ratio of the cell numbers in two main groups was the deduced from these karyometric studies. On the first diagram (Fig. l a , b, c) the data of the three layers (A, A 1; B) were plotted separately. In the layers A and Aj a possible separation of two groups of dots presents itself at the value of log. volume of 2.4. The two groups of the dots, both in layers A and Ax are elongated parallel with the direction of long diameter indicating the presence of spheroid and slightly ovoid nuclei in both groups, but further separation was not considered possible from these diagrams. The ratio of cell numbers falling into the two groups is about 1:2 (114:225 and 119:224 respectively in layer A and Ax). The dot diagram Fig. 1c represents the cells in layer B. The data of layer B are shifted to the left, i.e. both nuclei and cells as described by several authors ( G U I L L E R Y 1 9 6 6 , SZENTAGOTHAI et al. 1966) are smaller than in layers A and A v The smallest nuclear log. volume in cells still clearly identifiable as neurons is 1.9 in layer B, in layers A and A1 it was 2. The boundary between smaller and larger nuclei in layer B was found at the level of log. vo-

lume 2.2. The ratio of cell numbers between the two groups of nuclei, which appeared possible to be separated was also found to be 1:2 (89:180) as it was in layers A and Av The distribution in layer B of smaller and larger nuclei, in this display was also elongated, but lacking definite boundaries within the groups a further separation of the rounded and elongated nuclei was omitted. The numerical ratio of the two main types of neurons was established in more details in the graphs, in which the nuclear excentricity was plotted against log. nuclear volume (Fig. 2 a, b, c). This type of representation of the data is suitable for the separation of further subdivisions according to the sizes of nuclei on one hand, and to their shape on the other. The ratio of the two main groups proved to be 1:2 on these diagrams too. The numerical ratio found in layer A was 137:275, in layer A1 129:240 and in layer B 82:175. (The numbers are the averages of the data of three series.) For further subdivisions both the size and shape of nuclei may support the separation into subgroups. The nuclei, with an excentricity of between 1 and 1.4 are rounded, and those with excentricity of between 1.4—2 are elongated ones. In the layers A and Ax about 64% all of the measured nuclei are rounded and 36% are elongated.

PLASM A-NUCIEUS RELATION

•v

16 18 20 22 24

26 28 30 32 34

36 38 40 l.d/l240 mm

Fig. 3. Dot diagrams of cells data in layers A and A, of LGN. The relation of logarithm of surface of perikaryon and nucleus is dotted against the long diameter in mm.

Quantitative histological studies on LGN

The rounded and elongated nuclei could be separated only in the small group. The sizes of the elongated nuclei are somewhat larger, indicated by a small shift of the group to the right. The group of large nuclei can be separated only on the basis of their sizes, although the boundary between the two subgroups is somewhat ambiguous. Medium-size nuclei are between log. volumes 2.7—3.2. The nuclei above log. volume 3.2 belong to the group of large nuclei in layers A and A x . The numerical ratio of medium size to large nuclei is about 7 6 — 8 0 % against 24—20%. In both subgroups of nuclei there is a continuum of shapes from spheroid to the ovoid, although some rounded and ovoid clusters may suggest themselves. Making an arbitrary separation at elongation above the level of excentricity 1.4, about two thirds of medium size nuclei are rounded, the rest being ovoid. From the larger nuclei a somewhat larger percentage (70—75%) are rounded. In layer B comparably similar groups and subgroups can be found, however, the percentage of rounded and ovoid nuclei are fairly close to one another (57 — 43), there are more ovoid and even almost fusiform nuclei than in the two other layers. The diameters of 503 neurons were also measured in layers A and Av The data were plotted on diagrams (Fig. 3), where also two not sharply separated group of the dots may be distinguished. The ratio between the two groups of dots proved to be also about 2:1 (328 large and 175 small cells).

Discussion The more or less circumscribed two groups of dots found in the nuclear sizes by means of karyometric examination correspond with great probability to the main types of neurons in LGN: to the relay and Golgi I I type interneurons. This suggestion is based on the relatively stable volume ratio between nuclear and perikaryon size. In all the three layers the ratio of relay and interneurons was found to be close to 2:1. Further subdivisions were possible in both main cell groups according to the shape of the nuclei. In the Golgi stain the interneurons are unequivocally the smaller neurons. The smaller nuclei hence very probably correspond to the interneurons in the dot diagrams. On the basis of the axonal arborization pattern and to some extent on that of the dendritic pattern two subgroups of interneurons have been distinguished already earlier (TOMBOL 1966/67, 1969 b). The Golgi type I I a interneurons have rather rounded and the Golgi type l i b interneurons have ovoid cell bodies. In the dot diagrams (Fig. 2) smaller rounded and

197

slightly larger ovoid nuclei are separated relatively clearly, corresponding probably to the two types of interneurons found in the Golgi pictures. The transitional zone between the two groups is not clearly defined in the dot diagrams but this was to be expected. The ratio between the rounded and ovoid cell nuclei is about 2:1 in all layers. This number, of course, indicates the ratio of nuclei with different shapes only and it is not necessarily the exact ratio of the two types of interneurons. In the case of the large cells the separation according to the size by karyometric measurements of two subgroups is less ambiguous. The Golgi pictures show the presence of large radiate type and medium size (principal) relay neurons ( G U I L L E R Y 1 9 6 6 , S Z E N T A GOTHAI et al. 1 9 6 6 , T O M B O L 1 9 6 6 / 6 7 ) . The medium size or principal neurons may have rounded or ovoid cell bodies, while the large radiate relay cells are mainly rounded. The smaller number of large ovoid nuclei may belong to the large ovoid (fusiform) neurons which were characterized (TOMBOL 1968, TOMBOL et al. in press) as interlaminar reticular cells, very probably belonging to the diencephalic reticular system. The overall cell number in the LGN is 5.59 x 10 5 on the average (MADARASZ et al. in press). Two thirds of the cells are relay (3.73 X 10 5 ) and one third interneurons (1.86 X 10 5 ). It is interesting to examine the distribution of the two main types of neurons in the different layers: in layer A there are 1.88 x l O 5 , in layer A j 1.36 X 10 5 and in layer B 4.8 x l O 4 relay neurons. In layer A the interneurons are 9.4 x l O 4 , in layer A1 6.8 X 10 4 and 2.4 x 10 4 in layer B (Table I). A certain portion of the interneurons are Golgi type l i b cells with longer axons. On the basis of karyometric results and their analysis by appropriate graphic display it can be assumed that about one third of interneurons contacts neurons in neighbouring layers. The profuse axonal arborization of the Golgi type l i b of the interneurons has local connections — also with initial segments of the axons of principal neurons (Fig. 4) — and in a neighbouring layer as well, mostly with different dendrites. The Golgi type I I a interneurons have an exceptional position in the network of LGN both with respect to their numerical representation and to their morphological characteristics. About 40—50 claw-shape axon terminals are arranged locally in clusters and in general within fairly large discs (of 400—600 |xm and 100—150 [¿m diameters), oriented in parallel with their dendritic tree. Considering the density of neurons and the probable intersections with the dendritic ramification of relay cells (following paper IV.) on one hand, and the spatial distribution of the claw-shape terminals on the other, it

198

Madarasz, M., J . Gerle, F. Hajdu, Gy. Somogyi and T. Tombol

Fig. 4 a, b, c. Contact between principal neuron and Golgi I l / b interneuron. a) The arrow points the axonbranche of interneuron curving round the initial part of axon of the principal neuron, b, c) show the further axonarborization and terminals of the interneuron.

Quantitative histological studies on LGN

199

Fig. 5 a, b. Dendritic appendages (dp) and axonterminal (t) of interneuron in close contacts the principal neurons, c) Dendritic appendages (dp) of Golgi I l / a interneuron on t h e dendrites of large relay neuron, d) Dendritic appendages belonging to two interneurons in close contact each-other.

200

Madarász, M., J. Gerle, F. Hajdu, Gy. Somogyi and T. Tombol

clarified. Several authors think that their effect in the network of the LGN is mainly local (FAMI-

N : RN = 1=2

GLIETTI 1 9 7 0 , HAMORI et al. 1 9 7 4 , PASIK et al. 1 9 7 3 ,

-°*_ORN

-fr< 2

11N innervates12-15RN 6-8 IN converge on 1 RN

SZENTAGOTHAI

3

I RN innervatesU-5 IN 8-10 RN converge on 1 IN

o Á o O

J - O " * O

IN O

° O

O

f

O

o

o

Fig. 6. Schematic drawing of the interconnection of relay and interneurons. The empty circles represent the relay and the black spots represent the interneurons.

may be assumed that one Golgi type I I a interneuron contacts — by means of its axon terminals — several (12 — 1.5) relay neurons. These contacts, according to our observations, — for the time being only on the basis of Golgi pictures — are established mainly with the relay neurons, near the dendritic ramification points or on the cell body. The other morphological peculiarity of Golgi type I I a interneurons are their 40—60 dendritic appendages (complex spines or spine-clusters). These appendages are important components of synaptic glomeruli (FAMIGLIETTI 1 9 7 0 , FAMIGLIETTI a n d PETERS HAMORI et

al.

1974,

SZENTAGOTI-IAI

1973,

1972,

WONG-

RILEY 1972). Their number indicates, that they may have connections arranged in a relatively wide space: their dendritic arborization space is the same order as that of the optic afferents. This arrangement and the conjecture that several relay dendrites may join in the same glomerulus, the connections between Golgi II a interneurons and relay cells must be abundant (judged to be at least 1:40 — 60). The function of the axon terminals of interneurons is unclear, although they are considered with fair probability as of inhibitory nature. The role of dendritic appendages, which probably establish most of the dendro-dendritic synapses has not been properly

1973,

WONG

1970).

The

dendritic

appendages of Golgi type II a interneurons contact both types of relay neurons according to the Golgi pictures (Fig. 5). The function of the interneurons gets even more complicate considering the contacts of Golgi l i b interneurons in the parent and also in t h e n e i g h b o u r i n g l a y e r s (SANDERSON et al. 1 9 7 1 ) .

In conclusion it can be said that the interneurons in the' LGN have widespread connections with both types of relay neurons and the numerical data of morphological observations are in accord with the results of physiological studies according to which about 5 — 6 interneurons might converge on each principal neuron (BURKE and SEFTON 1966). This relation may be explained with the extensive contacts between interneurons and relay neurons, which according to the above speculations based on the numerical relations, densities and the number of contact sites is in the same order (6 — 8 interneurons converge on one relay cell) (Fig. 6). The connections between the relay and interneurons are mutual. The initial collaterals of principal neurons contact mainly the interneurons (TOMBOL 1966/67, 1968). Golgi observation — based on

rapid Golgi stained specimens — show rather poorly arborizing initial collaterals of the relay neurons. The maximal number of such connections that may be assumed on the basis of the number of i.e. terminals is 4—5. Reckoning with the double number of relay neurons, the 8:1 ratio of relay to — interneuron connectivity

(BURKE a n d SEFTON 1 9 6 6 )

is

very near to what is found in the Golgi pictures, if combined with the numerical ratio of relay to interneurons, i.e. 8 — 10:1 (Fig. 5). The separation of the relay neurons into two groups, and their numerical ratio appears to gain significance with respect to the different types of optic fibers (Y and X fibers) and to the two parallel optic systems from retina to the cortex (CLELAND et al. 1971) (which will be further discussed in the next paper (IV.) of this series).

References BURKE, W., and A. J. SEFTON : Inhibitory mechanisms in lateral geniculate nucleus of rat. J . Physiol. (Lond.), 187 2 3 1 - 2 4 6 (1966). CAJAL, S., Ramón y : Histologie du Systeme Nerveux de l'Homme et des Vertébrés, Vol. 2. Maloine, Paris, 1911. CLELAND, B . G., M. W. DUBIN and W. R. LEVICK: Sustained and transient neurons in the cat's retina and lateral geniculate nucleus. J . Physiol., 217, 4 7 3 - 4 9 6 (1971).

Quantitative histological studies on LGN E . V., Dendro-dendritic synapses in the lateral geniculate nucleus of the cat. Brain Research, 20 1 8 1 - 1 9 1 (1970). F A M I G L I E T T I , E . V . , and A . P E T E R S : The synaptic glomerulus and the intrinsic neuron in the dorsal lateral geniculate nucleus of the cat. J . comp. Neurol., 144, 285 — 334 (1972). G A R E Y , L. J . , and T. P. S. P O W E L L : The projection of the lateral geniculate nucleus upon the cortex in the cat. Proc. Roy. Soc. B . 169, 107 — 126 (1967). FAMIGLIETTI,

GROSSMANN, A . ,

A. R . LIEBERMAN

and

K.E.WEBSTER:

A

Golgi study of the rat dorsal lateral geniculate nucleus. J . comp. Neurol., 150, 4 4 1 - 4 6 6 (1973). G C I L L E R Y , R . W . : A study of Golgi preparations from the dorsal lateral geniculate nucleus of the adult cat. J . comp. Neurol., 128, 2 1 - 5 0 (1966). HAMORI, J . ,

P . PASIK,

T . PASIK

and

J.

SZENTAGOTHAI:

Triadic synaptic arrangements and their possible significance in the lateral geniculate nucleus of the monkey. Brain Research, 80, 3 7 9 - 3 9 3 (1974). K L U V E R , H., and E . B A R R E R A : A method for the combined staining of cells and fibres in the nervous system. J . Neuropath. E x p . N e u r . , 12, 4 0 0 - 4 0 3 (1953). O'LEARY, J . L . : A structural analysis of the lateral geniculate nucleus of the cat. J . comp. Neurol., 73, 405 — 430 (1940). L E O N T O V I C H , T . A . , and G . P . Z H U K O V A : The specificity of the neuronal structure and topography of the reticular formation in the brain and spinal cord of carnivors. J . comp. Neurol., 121, 3 4 7 - 3 8 0 (1963). MADARASZ, M . ,

J . GERLE,

F . HAJDU,

G y . SOMOGYI

and

T. T O M B O L : Quantitative histological studies on the lateral geniculate nucleus in the cat. I I . Cell numbers and densities in the several layers. In the press. MOREST, D . K . : Dendrodendritic synapses of cells that have axons: The fine structure of the Golgi Type I I in the medial geniculate body of the cat. Z. Anat. EntwickLGesch., 133, 216 — 246 (1971). PALKOVITS, M . , and J . F I S C H E R : Karyometric investigations. pp. 347. Akad6miai Kiado, Budapest, 1968. PASIK, P.,

T . PASIK,

J . HAMORI

and

J.

SZENTAGOTHAI:

Golgi type I I interneurons in the neuronal circuit of the monkey lateral geniculate nucleus. Exp. Brain Res., 17, 1 8 - 3 4 (1973). SANDERSON, K . J . : Visual field projection columns and magnification factors in the lateral geniculate nucleus of the cat. Exp. Brain Res., 13, 1 5 9 - 1 7 7 (1971). SANDERSON, K . J . ,

P. O. BISHOP

and

J.

DARIAN-SMILER:

The properties of the binocular fields of lateral geniculate nucleus. Exp. Brain Res., 13, 178 — 207 (1971). S C H E I B E L , M., and A. S C H E I B E L : Patterns of organization in specific and nonspecific thalamic fields. I n : D. P. PUR-

201

and M. D. Y A H R (Eds.) The Thalamus, Columbia University Press, New York and London, 1966, pp. 13 to 47. S H K O L N I K - Y A R R O S , E . G.: The structure of visual analyser and colour vision, Arch. Anat. Gestol. Embriol., 42, 12 — 30 (1962). In Russian, English summary. S Z E N T A G O T H A I , J . : The structure of the synapse in the lateral geniculate body. Acta Anat., 55, 166 — 185 (1963). S Z E N T Ä G O T H A I , J . : Lateral geniculate body structure and eye movement. I n : J . D I C H G A N S and E . B I Z Z I (Eds.) Cerebral Control of Eye Movements, Karger, Basel, Bibl. Ophthal., 82, 1 7 8 - 1 8 8 (1972). S Z E N T A G O T H A I , J . : Neuronal and synaptic architecture of the lateral geniculate body. I n : R . J U N G (Ed.) Handbook of Sensory Physiology, Vol. V I I / 3 B . , Springer Verlag, Heidelberg, pp. 141—176. S Z E N T A G O T H A I , J . , J . H A M O R I and T. T Ö M B Ö L : Degeneration and electron microscope analysis of the synaptic glomeruli in the lateral geniculate body. Exp. Brain Res., 2, 2 8 3 - 3 0 1 (1966). T Ö M B Ö L , T . : Short neurons and their synaptic relations in the specific thalamic nuclei, Brain Research, 3, 307 to 326 (1966/67). TÖMBÖL, T . : Synaptic architecture of specific thalamic nuclei Thesis, Budapest, 1968. In Hungarian. T Ö M B Ö L , T . : Terminal arborizations in specific afferents in the specific thalamic nuclei. Acta morph. Acad. Sei. hung., 17, 2 7 3 - 2 8 4 (1969). T Ö M B Ö L , T : T W O types of short axon (Golgi 2nd) interneurons in the specific thalamic nuclei. Acta morph. Acad. Sei. hung., 17, 2 8 5 - 2 9 7 (1969). PURA

TÖMBÖL, T . ,

M . MADARÄSZ,

F . HAJDU,

G y . SOMOGYI

and

J . GERLE: Quantitative histological studies on the lateral geniculate nucleus in the cat. I. Measurements on Golgi material. In the press. WONG, M. T. T . : Somato-dendritic and dendro-dendritic synapses in the squirrel monkey lateral geniculate nucleus. Brain Research, 20, 1 3 5 - 1 3 9 (1970). W O N G - R I L E Y , M. T. T . : Neuronal and synaptic organization of the normal dorsal lateral geniculate nucleus of the squirrel monkey, saimiri sciureus. J . comp. Neurol., 144, 2 5 - 6 0 (1972).

Address

of

authors:

Prof. Dr. med. Teriz T Ö M B Ö L 1st Department of Anatomy Semmelweis University Medical School Tüzoltö utca 58 1450 Budapest, Hungary

J . Hirnforsch, ig (1978) 2 0 3 - 2 1 2

1st Department of Anatomy, Semnielweis University Medical School, Budapest

Quantitative histological studies on the lateral geniculate nucleus in the cat. IV. Numerical aspects of the transfer from restinal fibers to cortical relay Ter6z

TOMBOL,

Magda

MADARASZ,

Gy.

SOMOGYI, F . H A J D U ,

J.

GERLE

With 4 figures (Received 7 t h July 1977)

Summary: The numerical data, gained both from the quantitative histology and Golgi stained material was completed with those of optic fibers. The number of X and Y fibers was estimated on the basis of our results, on the data of literature and from the ratio of the large and medium size relay neurons. The crossed and uncrossed fibers were counted and compared with the number of relay neurons in layer A and Aj. Knowing the different numerical and metrical counts of neuronal elements in LGN of cat some calculations were carried out on the overlaping of optic fiber arborizations, on the intersections of dendritic ramification points of relay neurons and on the spatial arrangement of both the optic terminals and the relay neurons. The comparison of the neumerical data on relay neurons and optic fibers and their relations were the basic factors of considerations on divergence and convergence of retinal input.

Introduction

the thick ones penetrate into the trilaminated dorsal nucleus. According to general interpretation (CAJAL

Quantitative observations on the cat LGN (MADA-

1911,

RASZ in press, TOMBOL 1969) were used f o r g a i n i n g

SZENTAGOTHAI 1 9 6 3 , 1 9 7 2 , 1 9 7 3 ) t h e t e r m i n a l a r b o r i -

some insight into the numerical relations of neuronal elements of LGN, such as cell numbers, densities and distribution of different types, as well as some metric parameters of LGN neurons as visible in Golgi stained specimens: the length of various dendrite categories, size and shape of arborization spaces, topological characteristics of the dendrites and corresponding data on the ramification of the retinal afferents. The data obtained in these previous studies are considered important for the understanding of the neuron network in the LGN. However, in order to get some insight into the transfer of optic signals to the cortical relay path it is necessary to complete the earlier numerical data with those of the optic fibers.

zations of thick fibers are confined to a single layer. Terminal arborizations of different retinal afferents may overlap. Although the rapid Golgi method is suitable to demonstrate total ramifications their sizes have not been measured in the classical studies. Also such measurements would have had a very limited value on the usual material of newborn animals. The perfusion Golgi-Kopsch procedure conversely stains the terminal parts of the optic arborizations, and this staining is probably near complete. However, the total ramification of one optic fiber is rarely revealed by aid of this technique (TOMBOL

In

earlier

studies

SZENTAGOTHAI

1963)

(CAJAL 1 9 1 1 , the

pattern

O'LEARY of

1940,

ramification

GAREY

and

POWELL

1967,

O'LEARY

1940,

1 9 6 8 , 1 9 6 9 , TOMBOL et al. in press).

In other studies counts of optic fibers were reported which fell into the same range in the cat (BISHOP 1 9 5 3 , BISHOP et al. 1 9 5 3 , 1 9 5 5 , BRUESCH a n d A R E Y 1942,

MEIKLE a n d SPRAGUE 1 9 6 4 ) , while

HUGHES

and

WASSLE

(1976)

found

recently

nearly

twice

of optic tract fibers, their morphological characteristics, distribution in space, and their synaptic relations were analysed, mainly in rapid GOLGI

more optic fibers under EM examination. The num-

stained

t h e i r sizes r a n g e b e t w e e n 0 . 5 — 1 2 ¡xm (BISHOP et al.

material.

O'LEARY

(1940)

observed

colla-

terals arising from the thin optic fibers and passing and terminating in the ventral nucleus of LGN; large optic fibers do not seem to issue collaterals to the ventral nucleus but always divide into thick and thin branches in the entry zone of the dorsal LGN. The thin primary branches disappear in the entry zone,

b e r of o p t i c fibers were f o u n d t o b e 1 1 9 , 0 0 0 , 1 2 0 , 0 0 0

and 127,000 respectively, they are myelinated and 1953).

HUGHES

a n d WASSLE

found

193,000

optic

fibers, the 53% of them belongs ot the thin category. HUBEL

and

WIESEL

(1962)

suggested

that

some

unmyelinated fibers may be present in the optic t r a c t . BISHOP et al. (1953) d e s c r i b e d t h e o p t i c n e r v e

contains about 120,000 fibers which range in axonal

204

Tómbol, T., M. Madarász, Gy. Somogyi, F. Hajdu and J . Gerle

diameter from 1 — 8.5 ¡¿m. The fiber-size spectrum shows evidence of grouping about axonal diameters of 1 — 1.5 (j.m and 4 — 4.5 pim, and according to their observation 80% of all fibers have diameters of 3 [xm or less than 3 [im. In studies on retinal ganglion cells, originally two types of cells were distinguished (CLELAND a n d al. 1 9 7 1 , 1 9 7 4 , HOFFMANN 1973) a n d

more recently three types were identified (BOYCOTT a n d WASSLE 1 9 7 4 , CLELAND a n d LEVICK 1 9 7 4 a , b ,

HOFFMANN 1973). These results have been confirmed by the retrograde tracing of cells with the horseradish peroxidase reaction (MAGELHAES CASTRO and MURATE 1976). The cells were classified as Y (or alfa), X (or beta) and W (or gamma) retinal ganglion cells and corresponding retinal afferents. The Y or alfa cells have their main connections in the LGN but their axon collaterals can be traced to the superior colliculus. The X or beta neurons establish contacts practically only the dorsal LGN, and probably some of their collaterals (estimated to be about 20%) enter the pretectal region (FUKADA 1971). The third type of retinal ganglion cells, the W (or gamma) cells are believed to send their axons only to the superior colliculus and to the midbrain reticular formation. The axons of the several retinal neuron types are in different ranges of thickness. In the optic tract the Y fibers are thick myelinated fibers, X fibers are of medium size and W fibers are thin. Some quantitative conclusions were also deduced from physiological findings (CLELAND a n d LEVICK 1 9 7 4 ) . 1 2 % of

all the observed cells in the retina are the gamma or W cells. 55% of the cells belong to the beta or X and 25% to the alfa or Y category of neurons. Another significant observation in this work is that the thickness of the axons of the Y and X neurons increases with the distance from the central area of the retina. The third numerical problem about the optic fibers is the decussation i.e. the ratio of crossed and uncrossed fibers. T h e m a j o r i t y of t h e studies (APTER 1 9 4 5 , DOTY 1 9 5 8 , HAYHOW 1 9 5 8 , MEIKLE a n d SPRAGUE

1964)

agree in the conclusion that about two thirds of the optic fibers are crossed in cat. Also according to POLYAK (1957) the rate of crossing of the optic

fibers varies between 50—70%. The objective of the present study was to obtain some numerical data in optic fibers and to combine the different quantitative data of the several neuronal elements and to make an attempt at interpreting them from the viewpoint of transmission through the LGN.

Materials and Methods The optic nerves and tracts from the same cats as were used for counting the cells and determine the volume of the nuclei ( K L Ü V E R and B A R R E R A 1 9 5 3 ) , after formaldehyde fixation were embedded into paraffin, then cut it transversal direction and stained with the method of M A R L E N E M C I L M O Y L ( 1 9 6 5 ) . In the stained and impregnated material the transsected fibers were counted under a rectangular grid with 1,600 X magnification. Four tracts and the nerves as controll of the same four cats were counted. To obtain information on the degree of fibers crossing, enucleations were made and after a survival of five months the fibers of both tracts and of the intact optic nerve of one cat were counted.

Results Counting was carried out on the total transection area of the optic nerves and tracts of each animal. Three categories of fibers (according to diameter) were counted separately. There was a small difference (110,500 in this study versus 120,000-127,000 in refs. 2, 3, 4, 29) between the number of optic fibers, which may be attributed to differences in the techniques. This work being aimed at gaining data of the fibers entering the dorsal LGN, emphasis is on the optic tract fibers. The number found in our material (110,500) is an average of four cats (one tract in each), the standard deviation was found t o be ± 1 , 1 0 0 , i.e. t h e r e l a t i v e deviation is 0 . 9 9 % . I n

view of the small variation in the number of fibers, it was deemed sufficient to separate the different caliber groups in one of the cases only. In the selected case the total number of fibers was 111,000. Three categories of fibers were counted: 4,100 thick myelinated fibers with diameters 4 or larger than 4 |j.m, 3,050 thin myelinated and unmyelinated fibers of less than 1 [xm diameter, the rest totalling 103,850 had their diameters between 1 fxm and 4 ¡¿m. The three groups of fibers correspond to those found in physiological experiments (BOYCOTT and WASSLE

1974,

ENROTH-CUGELL

CLELAND and

and

ROBSON

LEVICK 1966,

1 9 7 4 a,

b,

HOFFMANN

1973), however, their numerical ratio is slightly different (12% W, 55% X and 25% Y fibers according to CLELAND et al. versus the above demonstrate 2.7% thin, 3.7% thick and the rest is 93.6% fiber). The thick myelinated fibers (4,100) might belong to Y or alfa neurons, while the thin fibers may correspond to the W (or gamma) fibers. The remaining 103,850 fibers are probably shared between Y (or alfa) and X (or beta) fibers. The number of crossed and uncrossed fibers was counted in the optic tracts of an enucleated cat (in one cat both tracts). The crossed fibers were located in the medio-central part of the tract, while the un-

Quantitative histological studies on the LGN

crossed ones surround the crossed fibers ventrolaterally. The ratio of crossed fibers was found about 6 2 % ( 5 6 , 6 1 0 - 5 8 , 8 3 0 ) of the total number of fibers. The number of cells in layer A and A 1 ( in the 2 animals in which this was studied, was found to be 58:42 (in %) and 57.8:42.2 (in %) respectively (MADARASZ et. al. in press a, b). Hence, the cell numbers in the two main layers are in fair agreement with the degree of crossing in the optic chiasm. For an appraisal of the connectivity between optic terminals and relay neurons it is necessary to determine the space of arborization of individual optic fibers. In Golgi studies (TOMBOL 1968, 1969) the spans in the three perpendicular directions of total retinal afferent arborizations in layer A and have been measured. The axonal arbors were of different sizes but in view of the erratic selectivity of the G O L G I method only the largest axonal arbors were taken into account. Such arborizations of optic fibers were calculated to be around 7 x l 0 6 | x m 3 . The volume of layer A is 9.471 X 109 fxm3 (9.471 mm 3 ), that of layer Aj is 6.883 X10 9 (xm3 (6.883 mm 3 ) and the total volume of both main layers is 16.354 X 109|i.m3 (16.354 mm 3 ). B y dividing the total volume of both layers with the volume of the largest observed arborizations we arrive at a figure giving the number of optic arborizations (2315) that would fit into the layers if it were assumed that the arbors do not overlap. Finally the total number of fibers divided by this theoretical number would show the degree of overlap of retinal afferent arborizations (47). The first theoretical figure is 1341 i.e. so many axonal arbors would fit into layer A without overlap, taking into account the real number of crossed fibers (62,611) this shows a 46.7 — fold overlap. The equivalent figures for A x are 974 arbors without overlap, and therefore there must be a 46.5 — fold overlap of the uncrossed fibers (45,339). The two main layers together would contain 2315 non overlaping arborization spaces, therefore 46.6 (47) optic fibers would arborize in any given space of this size. 107,950 optic fibers (Y and X fibers) enter the layers A and Aj of the dorsal LGN. These fibers give off collaterals to layer B. The assumed W fibers pass on to the superior colliculus and the midbrain reticular formation. 5 8 % (62,611) of the optic fibers entering the LGN, are crossed ones, which supply layer A ( 1 . 9 X 1 0 5 relay neurons). The remaining 4 2 % (45,339) of the optic fibers are uncrossed, which terminate in layer A1 ( 1 . 4 x 10 5 relay neurons). The volume of layer B is 3.485 mm 3 . The arborization space of optic fibers is much smaller in this layer. The largest measured space of an axonal arborization was about 3 X 1 0 6 ¡xm3. According to these data 1161 arborization-spaces of this size could be arranged Hir nforschung, B d . 19, H e f t 3

205

without overlap in lamina B . Since the number of collaterals emitted by the Y and X is completely unknown, the probable overlap can not be estimated in this layer. Knowing the size (in layers A and A x ) of axonal arborization spaces of the optic fibers the number of relay neurons fitted into the same space can be deduced. In this calculation we have to assume, of course, that the dendritic trees of relay neurons interpenetrate. According to the density counts given in preceding papers (MADARASZ et al. in press) 140.4 relay neurons are contained in layer A and 139.8 relay neurons in layer A1 (in the two layers together on average 140) are located in the space of one larger retinal fiber arborization (Fig. 1). In the same space there are 70 Golgi type I I interneurons in layers A and A x respectively.

Discussion 1. The number and distribution

of optic

fibers

Comparing our data with those of the literature (BISHOP

1953,

BISHOP

et

al.

1953,

1954,

BOYCOTT

a n d W A S S L E 1 9 7 4 , C L A R E e t a l . 1 9 6 9 , CLELAND e t a l .

1971, 1.974a, b, HAYHOW

1958,

ENROTH-CUGELL HOFFMANN

and

1973,

ROBSON MEIKLE

1966, 1964)

concerning the number of optic fibers a relatively small difference of 8 — 1 4 % was observed. A more significant numerical difference was found in the number of thin (W or gamma) fibers. In our material the thin fibers contributed only to 2 . 7 % of the total optic tract fibers, while CLELAND et al. (1974b) found about 1 2 % gamma cells (so called sluggish units) in retina, the axons of which are probably identical with the thin fibers. These fibers are not only very delicate but some of them are unmyelinated and hence not so easily stained. Their slow conduction velocity is well known (BISHOP et al. 1953). The smaller number of thin fibers in our counts may be due to the magnification 1600, which may have been too low to detect all of the thin fibers. The lower number in the total counts of optic tract fibers (about 1 0 % and 8 0 % respectively) might be explained with the difference in the number of thin fibers found in our material. In the counts presented the number of thick (Y or alfa) fibers was 4,100. Conversely the alfa cells of retina were found to contribute to 2 5 % of the cells by C L E L A N D et al. (1971, 1974 a, b). Another important conclusion of this work is that the thickness of the axons of both alfa and of beta ganglion cells increases continuously from the central area towards 15

206

Tombol, T., M. Madarasz, Gy. Somogyi, F. Hajdu and J . Gerle

OR

372,759

Ai

B

0T 107,950

(YandX) FIBERS

47

OPTIC FIBERS

140

RELAY NEURONS Fig. 1. Schematic drawing from a coronal segment of LGN, from the' arborization space of one optic fiber and from three relay neurons in the same space without overlaping. OT = optic fibers, OR = optic radiation. 1 = first order preterminal fiber, 2 = preterminal bouquet (terminal unit), 3 = bouton cluster (terminal portion).

Quantitative histological studies on the L G N

Fig. 2. Coronal section of L G N . T h e neuronal arrangement is represented b y the different type of cells and fibers found in t h e three main layers of the nucleus. 1 = large relay neuron, p = principal neuron, a = Golgi I l / a interneuron, b = Golgi I l / b interneuron, o = optic fiber arborization, c = corticogeniculate fiber, r = medium calibre fiber with various side branches.

the periphery. On the basis of this observation one might suppose that the transition in thickness between Y and X fibers is continuous and the two types of fibers show considerable overlap in size distribution. The results of nuclear-volume analysis nearly established the percentage of the two types of relay neurons in the LGN. The ratio between the large and medium size relay neurons is about 1:4 i.e. 20 — 24% of relay neurons may belong to the large radiate cell category (MADARASZ et al. in press). It might be significant that percentage of the large relay cells is similar to that of Y fibers and it

207

should be kept in mind that these neurons have contacts with other cortical areas than the medium size or principal neurons ( G A R E Y and P O W E L L 1 9 6 7 ) . The numerical and morphological data are also matched by the physiological findings (CLELAND et al. 1971). Two separate systems seem to exist between the retina and visual cortex; one having so called "transient" and the other "sustained" transfer characteristics. It might be an attractive thought to speculate that the one converged over the alfa (Y) cells, is primarily relayed through the large relay neurons. The other system of the beta (X) cells might be relayed by the principal neurons of the L G N . O ' L E A R Y ( 1 9 4 0 ) observed the entrance of thin fibers and of thick optic fiber collaterals into the midbrain tectum and reticular formation. The larger (1 —12 ¡¿m) fibers terminate in the LGN. In our results the combined average of Y and X fibers would be around 1.1 xlO 5 , from which about 2.1 x 10 4 —2.5 x 104 might be considered as Y fibers, while the rest of 8 . 3 - 8 . 6 X 1 0 4 may be the X fibers. 15*

208

Tombol, T., M. Madarasz, Gy. Somogyi, F. Hajdu and J. Gerle

2. General considerations A realistic interpretation of the function of a neuronal network depends on a basic understanding of interneuronal connections, geometry, topology and other kinds of arrangements of the network, arborization patterns of specific and nonspecific afferents, and on the fundamental quantitative aspects: ratios and spatial interrelations of the several neuronal elements. 2.2.

Considerations res of neuronal

of the fundamental organization

morphological

featu-

In an earlier network model of SZENTAGOTHAI ( 1 9 6 7 ) the distribution of dendritic and axonal ramifications in the specific thalamic nuclei was considered as lacking any regularity. It was subsequently shown by T O M B O L ( 1 9 6 9 ) that the distribution of the major elements in axon arborizations are not quite "random" in relation to the relay neurons but may have certain features of specificity in arrangement. The cellular elements show a quasi columnar arrangement in the G O L G I stain. The expansions of the dendritic trees of the principal neurons, and both of the dendritic and axonal arborizations of the interneurons show a preferential vertical orientation relative to the laminar plane. The larger the surface expansion of the lamina, the more pronounced becomes the columnar arrangement (Fig. 2). At the laminar borders next to the dorsal surface of the LGN and particularly in layer B the arrangement of neuronal elements is not regular and the same is experienced at the rostral and caudal ends of the nucleus. The arborizations of the optic fibers have also some preference for certain directions and the course of cortico-geniculate fibers transgressing several layers show an impressive vertical columnar orientation. The two main afferent fiber-systems, the retinal afferents and the descending cortico-geniculate projection appear to be subject to the geometrical distortions corresponding to the curvature of the laminae. On coronal sections their direction is almost completely radiate, on sagittal section the orientations of the neuropil fit the S-shape of the nucleus. This was most clearly shown already in the impressive diagram of T E L L O ( 1 9 0 4 ) .

2.2.

Considerations zations

of the organization

of optic fibers

arbori-

The arborization space of one optic fiber is the obvious structuro-functional unit in the LGN, from which all speculations might originate and into which all types of neuronal elements can be placed and where the connections can be characterized by nume-

rical data. This mental strategy will be followed subsequently. Earlier observations (TOMBOL 1968, 1969) on the size of optic fiber arborization spaces were confirmed in present study (TOMBOL et al. in press). The arborization space (the largest measured) was about 7.4 X10® [¿m3. Connectivity relations of the retinal afferents are based, in addition to the size of their arborization space, also on relevant details of their arborization patterns. The total of about 80 boutonclusters ("terminal portions"), given by one optic fiber, are generally grouped into clusters i.e. preterminal bouquets ("terminal units" — about 10 per afferent). The sizes of space of preterminal bouquets (terminal units) are corresponding to the intersection area of ramification points of relay dendrites. On the basis of such an arborization pattern it is possible to surmise that the terminal arborization pattern of retinal afferent (with its preterminal bouquets and bouton clusters) might be the fundamentally determinant factor in divergence and convergence of optic impulses.

2.3.

The probable degree of "divergence" relay

in the

retino-genicular

The divergence in the genicular relay depends on several factors: on the number of terminals of one optic fiber, on the grouping of these terminals (on the number of "preterminal bouquets") and on their spatial interrelations with the ramification points of relay dendrites, which have been recognized as the strategic points of the optic transmission. In one large arborization space 140 relay cells are localized in both layers A and A r Since one relay neuron has about 18 dendritic ramification points on average (TOMBOL et al. in press) and the number of optic fibers terminating in the same volume is 47 in both layers A and A x , one retinal afferent — having about 80 bouton clusters (terminal portions) — may theoretically contact from three to 80 relay neurons as the two extremes. It has to be notice — considering the divergence — the ratio between optic fibers and relay neurons, is 1 : 3 . This would be, of course, the divergence of incoming optic impulses, if neither the preterminal bouquets (terminal units) localizations, nor the dendritic intersections were taken into consideration. In the following speculation the significance of the dendritic ramification points has to be emphasized. Each of the relay neurons has about 18 ramification points shown to be favoured sites for connections with specific afferents. The space encompassing the arborization points of a relay neuron has, therefore, been labeled the "specific active dendritic space".

Quantitative histological studies on the LGN

209

t

LI OPTIC FIBERS Fig. 3. Schematic drawing on relationship of optic fibers and relay neurons. The given numbers of optic fibers and relay neurons are found in t h e arborization space of one optic fib er (rp = dendritic ramification points).

The degree of spatial overlap (i.e. howemany "specific active dendritic space" share in the same volume) of dendritic ramification points can be calculated

on the basis of available data. In the arborization space of one optic fiber the "active zones" of two or three relay neurons can be accomodated without having to interpenetrate. However, the total number of relay neurons in such a volume of tissue space is 140 on the average. Calculating with the probability that the maximum of interpénétrations by relay dendrites is about 3 (i.e. the ramification points of

210

Tombol, T., M. Madarasz, Gy. Somogyi, F. Hajdu and J . Gerle

DIVERGENCE

30

same optic arborization space may contact the 140 relay neurons present. For arriving some reasonable estimate of convergence it seems necessary for compute data on the preterminal bouquets (terminal units) of optic fibers, with the degree of interdigitation of dendritic tufts (ramification points), and with the number of ramification points per relay neuron. The ratio of the number of preterminal bouquet ("terminal units") of 47 optic fibers present in the arborization space and the number of relay neurons (in the same space = 140) reduced by the possible interdigitation (3 X ) indicates a convergence in a moderate manner 47 optic fibers x 10

Fig. 4. Schematic drawings on the basic connections which define both the divergence and convergence of retinal afferents in lateral geniculate nucleus (LGN). OF = optic fiber, 11N = relay neuron, ic = initial collateral, IN = interneuron, O terminals = optic terminals, R dendrit = relay dendrite.

140 relay neurons

=10

3 According to this speculation the convergence is about 10, i.e. about ten optic fibers may contact one relay neuron (Figs. 3, 4). 3. Concluding remarks

three relay dendrites can interdigitate with one another), and with the about ten preterminal bouquets (terminal units) of one optic fiber arborization, 30 relay neurons can be assumed to receiving contacts from one of the larger optic arborizations (i.e. 10 preterminal bouquets (terminal units) multiplied with the maximum of intersections of relay dendritic ramification points). In this speculation about the divergence two decisive factors had to be considered: the arborization pattern of a single larger retinal afferent, and the probable degree of interdigitation by the dendrites of relay cells. The degree of divergence (1:30) obtained by this speculation is felt to be realistic of one considers matters intuitively in the knowledge of the Golgi picture. The diagrams (Figs. 3,4) and the numbers given refer to the larger afferents, so that they have to be reduced proportionally if smaller afferents and less intersections of dendritic ramification points are considered (1:30, 1:20, 1:10). 2.4.

The probable afferents

convergence

on the relay cells of

retinal

For the speculation about convergence partly the same factors (the arborization pattern and size of optic fibers, the dendritic arborization pattern of relay neurons and the interdigitation of their dendritic tufts) have to be considered, however, additionally the number of optic fibers arborizing in the same space has to be taken also into account. Theoretically the 47 optic fibers with 80 bouton clusters (terminal portions) (3,760 altogether) each in the

The numerical data, gained both from the quantitative histology and from representative measurements made on GOLGI stained material provide a better insight into the connectivity of the LGN. I t should be appreciated that the network model emerging from this study and speculations added have their limitations, mainly in consequence of the representative nature of the measurements on G O L G I material. I t is calculated that the sharing of 47 optic fibers in the arborization space of one retinal afferent and the intersection of dendritic ramifications, of 140 relay cells in the same space, result in a divergence of around 30 and a probable convergence of 10, in spite of a theoretical maximum of divergence of 140 and convergence of 47 as would appear from the more presence of the respective cells and arborizations in the same volume. It is interesting to ponder about the relatively high divergence as compared to the relatively low convergence resulting from the data and the further reasonings. The value of divergence deduced here surpasses the objective impression, but considering that it applies to the largest afferents, we are confident that it is realistic. The relatively low degree of convergence is even more baffling, however, here the relatively low numbers — as compared to that of the relay cells (the raugh numerical ratio of optic afferents to relay cells is 1:3 in both main layers, i.e. layer A:188,338 relay neurons and 62.611 optic fibers, layer A 1 :136,231 relay neurons and 45,339 optic fibers) has to be considered.

Quantitative histological studies on the LGN

The numerical data on relay neurons and the optic fibers and their spatial arrangement will have to be completed later by data on the interconnections b e t w e e n r e l a y cells a n d i n t e r n e u r o n s

(BURKE

and

1966a, b, c, SANDERSON 1971, SANDERSON et al. 1971, SINGER and C R E U T Z F E L D T 1970). Even though their ratio being known (2:1) as well as some data are available about their possible contacts (vice-versa), there are many crucial details of fine synaptology (glomeruli, triadic structures, dendritic synapses, etc.) that need an elucidation by quantitative electron microscopical method so this is being done in this laboratory. This is as far as it is felt that one can go on the level of the light microscope and the network model here proposed should be considered as being in a preliminary intermediate stage. SEFTON

References Projection of the retina on the superior colliculus of cats. J . Neurophysiol., 8, 1 2 3 - 1 3 4 (1945). B I S H O P , P. O. : Synaptic transmission. An analysis of the electrical activity of the lateral geniculate nucleus in cat following optic nerve stimulation. Proc. Roy. Soc. B., 141, 3 6 2 - 3 9 2 (1953). B I S H O P , P. O., D. J E R E M Y and J . W. L A N C E : The optic nerve: properties of a central tract. J . Physiol. (Lond.), 121, 4 1 5 - 4 3 2 (1953). B I S H O P , G. H., and M. H. C L A R E : Organization and distribution of fibers in the optic tract of the cat. J . comp. Neurol., 103, 2 6 9 - 3 0 4 (1955). B O Y C O T T , B . B . , and H . W Â S S L E : The morphological types of ganglion cells of the domestic cat's retina. J . Physiol., 240, 3 9 7 - 4 1 9 (1974). B U R K E , W . , and A . J . S E F T O N : Discharge patterns of principal cells and interneurons in lateral geniculate nucleus of rat. J . Physiol. (Lond.), 187, 2 0 1 - 2 1 2 (1966). B U R K E , W . , and A . J . S E F T O N : Recovery of responsiveness of cells of lateral geniculate nucleus of rat. J . Physiol. (Lond.), 187, 2 1 3 - 2 2 9 (1966). B U R K E , W., and A. J . S E F T O N : Inhibitory mechanisms in lateral geniculate nucleus of rat. J . Physiol. (Lond.), 187, 2 3 1 - 2 4 6 (1966). B R U E S C H , S. R., and L. B . A R E Y : The number of myelinated and unmyelinated fibers in the optic nerve of vertebrates. J . comp. Neurol., 77, 6 3 1 - 6 6 5 (1942). C A J A L , S . Ramôm y : Histologie du système nerveux de l'homme et des vertébrés. Vol. 2. Maloine, Paris, 1911. C L A R E , M . H . , W . M . L A N D A U and G . H . B I S H O P : The relationship of optic nerve fibre groups activated by electrical stimulation to the consequent central postsynaptic events. Exp. Neur., 24, 4 0 0 - 4 2 0 (1969). C L E L A N D , B . G., M. W. D U B I N and W. R. L E V I C K : Sustained and transient neurons in the cat's retina and lateral geniculate nucleus. J . Physiol., 217, 473 — 496 (1971). C L E L A N D , B . G . , and W . R . L E V I C K : Brisk and sluggish concentrically oganized ganglion cells in the cat's retina. J . Physiol, (bond.)., 240, 4 2 1 - 4 5 6 (1974a). C L E L A N D , B . G . , and W . R . L E V I C K : Properties of rarely

APTER, J . T . :

211

encountered types of ganglion cells in the cat's retina and an overall classification. J . Physiol., (Lond.), 240, 457 to 492 (1974b). E N R O T H - C U G E L L , C . , and J . G. R O B S O N : The contrast sensitivity of retinal ganglion cells of the cat. J . Physiol. (Lond.), 187, 5 1 7 - 5 5 2 (1966). DOTY, R . W . : Potentials evoked in cat cerebral cortex by diffuse and by punctiform photic stimuli. J . Neurophysiol., 21, 4 3 7 - 4 6 4 (1958). F U K A D A ; Y . : Receptive field organization of cat optic nerve fibers with special reference to conduction velocity. Vision Res., 11, 2 0 9 - 2 2 6 (1971). G A R E Y , L. J , , and T. P . S. P O W E L L : The projection of the lateral geniculate nucleus upon cortex in the cat. Proc. Roy. Soc. B „ 169, 1 0 7 - 1 2 6 (1967). H A Y H O W , W. R . : The cytoarchitecture of the lateral geniculate body in relation to the distribution of crossed and uncrossed optic fibers. J . comp. Neurol., 110, 1 — 64 (1958). H O F F M A N N , K. P . : Conduction velocity in pathways from retina to superior colliculus in the cat. J . Neurophysiol., 36, 4 0 9 - 4 2 4 (1973). H U G H E S , A . , and H . W Ä S S L E : The cat optic nerve: fibre total count and diameter spectrum. Comp. Neurol., 169, 1 7 1 - 1 8 4 (1976). H U B E L , D. H . , and T . N . W I E S E L : Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J . Physiol. (Lond.), 160, 1 0 6 - 1 5 4 (1962). K L Ü V E R , H . , and E . B A R R E R A : A method for the combined staining of cells and fibers in the nervous system. J . Neuropath. Exp. Neur., 12, 4 0 0 - 4 0 3 (1953). O ' L E A R Y , J . L . : A structural analysis of the lateral geniculate nucleus of the cat. J . comp. Neurol., 73, 405 — 430 (1940). MADARÄSZ, M . ,

J . GERLE,

F. HAJDU,

G y . SOMOGYI

and

T. T Ö M B Ö L : Quantitative histological studies on the lateral geniculate nucleus in the cat. I I . Cell numbers and densities in the several layers in the LGN. In the press. MADARÄSZ, M . ,

J . GERLE,

F . HAJDU^

G y . SOMOGYI

and

Quantitative histological studies on the lateral geniculate nucleus in the cat. I I I . Distribution of different types of neurons in the several layers of LGN. In the press. T . TÖMBÖL:

MAGALHÄES

CASTRO, H . H . ,

L . A . MURATE

and

B . MAGAL-

Cat retinal ganglion cells projecting to the superior colliculus as shown by horseradish peroxidase method. Exp. Brain Res., 25, 5 4 1 - 5 4 9 (1976). M C I L M O Y L , M . : Two neurological staining techniques utilizing the dye Luxol Fast Blue. Canad. J . Med. Technol., 1 1 8 - 1 2 3 (1965). M E I K L E , Th. H . jr., and J . M . S P R A G U E : The neural organization of the visual pathways in the cat. In: C. C. P F E I F F E R and J . R. S M Y T H I E S (Eds.) International Review of Neurobiology, Vol. 6. Acad. Press, New York and London, 1964, pp. 1 4 9 - 1 8 9 . POL YAK, S.: I n : The vertebrate visual system, H. Klüver (Ed.) University of Chicago Press, Chicago, 1957. S A N D E R S O N , K. J . : Visual field projection columns and magnification factors in the lateral geniculate nucleus of the cat. Exp. Brain Res., 13, 1 5 9 - 1 7 7 (1971). HÄES

CASTRO:

SANDERSON, K . J . , P . O. BISHOP a n d J . DARIAN-SMITH: T h e

properties of the binocular fields of lateral geniculate nucleus. Exp. Brain Res., 13, 1 7 8 - 2 0 7 (1971). S I N G E R , C., and O . D . C R E U T Z F E L D T : Reciprocal lateral inhibition of on and off centre neurones in the lateral geniculate body of the cat. Exp. Brain Res., 10, 311 — 330 (1970).

212

Tömböl, T., M. Madarász, Gy. Somogyi, F. Hajdu and J . Gerle

J . : The structure of the synapse in the lateral geniculate body. Acta Anat., 55, 166 — 185 (1963). S Z E N T Ä G O T H A I , J . : Models of specific neuron arrays in thalamic relay nuclei. Acta morph. Acad. Sei. hung., 15, 1 1 3 - 1 2 4 (1967). S Z E N T Ä G O T H A I , J . : Lateral geniculate body and eye movement. In: J . Dichgans and E. Bizzi (Eds.) Cerebral Control of Eye Movements. Karger, Basel, Bibl. Ophthal. Vol. 82, 1 7 8 - 1 8 8 (1972). S Z E N T Ä G O T H A I , J . : Neuronal and synaptic architecture of the lateral geniculate body. In: R. Jung (Ed.) Handbook of Sensory Physiology, Vol..VI1/3. Springer Verlag, Berlin, 1973, pp. 1 4 1 - 1 7 6 . TÖMBÖL, T.: Synaptic architecture of specific thalamic nuclei. Thesis, Budapest, 1968. (In Hungarian.) TÖMBÖL, T . : Terminal arborization in specific afferents in the specific thalamic nuclei. Acta morph. Acad. Sei. hung., 17, 2 7 3 - 2 8 4 (1969). SZENTÄGOTHAI,

TÒMBÒL, T . :

M . MADARÁSZ,

F . HAJDU,

G y . SOMOGYI

and

J . GERLE, Quantitative histological studies on the lateral geniculate nucleus in the cat. I. Measurements on Golgi material. In press. T E L L O , J . F. : Disposición macroscopica y estructura de cuerpo geniculado. Trab. Lab. Invest. Biol. Univ., Madrid, 3, 3 9 - 6 2 (1904).

Address

of

authors:

Prof. Dr. med. Ter6z T Ö M B Ö L 1st Department of Anatomy Semmelweis University Medical School Tüzoltö utea 58 1450 Budapest (Hungary^

J . Hirnforsch. 19 (1978) 2 1 3 - 2 8 8

C. und O. Vogt — Institut für Hirnforschung der Universität Düsseldorf (BRD) (Direktor: Prof. Dr. A. HOPF)

The Accessory Optic System and the Retino-Hypothalamic System. A Review. By Jiirgen K. MAI With two figures and one table (Received May 27 th 1977)

Summary: The introduction of new techniques in neuroanatomy has helped to clarify a number of important issues on the nature of the accessory optic and retino-hypothalamic system. In this study, an effort was made, to collect all data obtainable, and to arrange them on the basis of some common parameter, so that the various results may be directly compared. These data were then interpreted on specific issues, although only limited coverage has been given to functional aspects, as described in older publications. The absence of a universally accepted concept of the function of both systems to date suggests the need for a thorough analysis of both contemporary and older literature dealing with a characterization of the structural components of the accessory optic and the retino-hypothalamic systems. On the basis of these anatomical studies it is concluded that the accessory optic system (AOS) is much more complex than formerly believed. Its development in various vertebrate classes is quite different. Among the mammals, the AOS is very well established in rodents but in primates and man its anatomical and functional role seems markedly reduced. In the rodents it consists of both superficially and deeply arranged axons which are in close topical relation to the cerebral peduncles. The axons not only supply the classic accessory optic terminal nuclei but also the subthalamic nucleus and the substantia nigra. The secondary projections have not yet been established. The retino-hypothalamic system (RHS) mainly but not exclusively supplies the suprachismatic nucleus (sc). Crossed as well as uncrossed retinal fibres project to the ventro-lateral and to the posterior part of this nucleus. The cells within the sc combine both secretory and neuronal properties. The possible functions exerted are discussed. Both, the AOS and the RHS, are so closely related within the suprachiasmatic area that most methods fail in correlating experimental results with either system. The numerous problems which still remain to be clarified are also discussed.

Introduction

Our morphological knowledge concerning the connectivity between various structures of the optic system is based mainly on degeneration studies.- In spite of methodological improvements, however, numerous contradictory findings demonstrate that the limits of the capacity of the degeneration methods have been achieved. New possibilities in evaluating neural connectivity were opened by physiological procedures, not disturbing the functional state of neurons by mechanical lesions. Among these methods, those utilizing axonal transport of radioactively labelled material hold an eminent place, if the distribution of retinal fibres is studied. Moreover, functional alterations are indicated by changes in silver grain (SG) density, thus adding some new functional perspectives to neuronal topography. The reliability of the autoradiographic method (ARG) has encouraged several authors to reexamine the connectivity of the optic pathways and to compare the results obtained with

those of earlier investigations. In order to arrive at an understanding of the connectivity pattern within the accessory optic (AOS) and the retino-hypothalamic system ( R H S ) 1 , it seems necessary to correlate the various foregoing reports, reflecting the huge amount of heterogenous material and methods by the experimental conditions applied. Inconsistencies may serve in the "differential diagnosis" of the results obtained today and may help in interpreting interspecific variations. The table discloses that the advent of improved neurohistological procedures (MARCHI and ALGERI,

1885;

NAUTA,

1.951;

HEIMER,

1967 b),

enabling the selective representation of single optic neurons until their terminal distribution has occasioned a considerable increase in the volume of harmonizing literature. Whereas formerly our greatest efforts were devoted to resolving methodological 1 Some authors include the RHS in the AOS (GIOLLI, "1961, 1 9 6 3 ; BAN e t a l „ 1 9 6 5 ; KNAPP a n d KANG, 1 9 6 8 ; MARG,

1973). Terminological reasons and morphological and functional peculiarities recommend a separation of both systems within this study.

214

Mai,

J. K .

considerations, at present the problems of interpretation stand out as the most significant task. Several reviews about either the AOS or the R H S have already been written in the past. None of them, however, has really matched the crucial aspects in comprising the vast literature of both systems. In the submitted table the interdependence between results obtained from the various animals used and the technical and analytical methods applied can be recognized. In spite of the limited reliability of earlier studies, this review is not restricted to "accepted" literature. Some results, gained by methods not accepted in view of our updated knowledge, have anticipated subsequent results despite failing conclusiveness. Others esteemed to be incorrect in our view, are included because they influenced terminology. The incorrect use of references has caused confusing nomenclature. It is therefore not surprising that identical names have been given to topographically different pathways. Comparison is further complicated by the fact that the homologies of some topographically similar neural groups receiving visual input may still be a matter of controversy (e.g. the preoptic-/suprachiasmatic area). The use of the same terms for these neural areas may easily create speculations about homologies and related functions. Therefore, it has been found most convenient to cite the anatomical pathways and related nuclei whenever possible, in the terms of the original contributions. Therein lies a prerequisite of the achievement of a common scheme of the AOS and R H S in various vertebrates with a standardized nomenclature. If this description has succeeded in analysing the extent to which connections are obtained and in interpreting the connectivity pattern, it may draw attention to some of the problems that remain to be solved before the organization of the AOS and the R H S can be understood. In a following paper, our autoradiographic investigations on the direct optic projections and on the interrelationship of some nuclei will be presented. 1. The accessory optic system (AOS) 1.1. Trajectories of the so-called pupillary fibres Closely related to earlier descriptions of optic fibre connections to areas other than the lateral geniculate body (cgl) and the optic tectum have been studies concerned with the pupillary reflex. Based on the identification of "coarse" fibres (v. GUDDEN, 1 8 7 0 , 1 8 8 5 , 1 8 8 7 ; v. BECHTEREW,

1894;

isolated from the main optic tract ( H E N S C H E N , 1 9 1 0 ; N O L L , 1 9 2 2 ) , a specific component,

WINKLER, 1918),

mediating the pupillary reflex, was described. The fact that neither the complete ablation of the superior colliculi (leaving the ventral wall of the central periaqueductal gray intact) ( K N O L L , 1 8 6 9 ; v. B E C H T E REW,

1883;

DARKSCHEWITSCH,

1887;

LEVINSOHN,

nor the removal of the lateral geniculate bodies (PFEIFER, 1930) produced substantial disturbances in pupillary light reaction was regarded by many authors as indicative that the pupillary fibres bypassed these structures. They consequently postulated that these fibres either separate in front of the cgl or deviate in medial direction through the lateral geniculate capsule or the basal medullary layer of the cgl towards the central gray before entering the oculomotor nuclei. 1909),

The various studies performed to demonstrate the "missing link" of the oculomotor reflex arc have to be regarded as a peculiar entity pertinent to the studies of the non-visually functioning optic nerve components. Some authors suggested that the pupillary fibres leave the optic pathway at the ventral diencephalon next to the tuber cinereum (v. B E C H T E R E W , 1 8 8 3 ; FLECHSIG, 1 8 8 6 ;

BOGROW,

1892,

BOCHENEK,

1894);

others followed fibres separating after the optic tract fibres have splitt off to immerse within the dorsal part of the lateral geniculate body (cgld) (STILLING, 1882 ; DARKSCHEWITSCH, 1 8 8 7 ; MAGNUS, 1 8 8 8 ) .

Still others found the pupillary fibres to emerge from the deep layers of the dorsal tectal area (MEYNERT,

1872;

SCHWALBE,

Ross,

1886;

BERNHEIMER,

SIEMERLING,

1891;

1881;

MASSAUT,

KOLLIKER,

1889; 1896;

PERLIA,

1886; 1889;

OBERSTEINER,

1 8 9 6 ; MOELI, 1 9 0 5 ) .

After the fibres had separated from the main optic tract, they were followed either superficially or deeply before ramifying within the oculomotor nucleus. In the first case they were found to swing around the cerebral peduncle (CC) ascending to the oculotmotor nuclei ( n l l l ) among the emerging oculomotor root fibres, or to penetrate the CC from the superficial aspect on their way to the n l l l . The deep pupillary fibres were described proceeding through the di- or mesencephalic periventricular gray. Among those most vigorously discussed were fibres proceeding with the bundles of the radiations of M E Y N E R T and their ventral prolongation, the fountaineous commissure of MEYNERT1, or fibres 1 T h e s e studies outlined t h e course of t h e bundles of t h e radiations of MEYNERT with t h e medial group of deep efferent t e c t a l (RILEY, 1943) or p r e t e c t a l fibres (CARPENTER and PIERSON, 1973) which directly p r o j e c t t o t h e oculomotor nucleus and whose stimulation usually is associated with pupillary dilatation (CROSBY and LAUER, 1959).

Accessory Optic and Retino-Hypothalamic System

passing with the ventral bundle of the posterior commissure1 ( D A R K S C H E W I T S C H , 1 8 8 6 ) . These investigations relied upon morphological examination of normal material, or experimental studies employing techniques without precise knowledge of the anatomical and functional model of the neuron and without considering artifacts accompanying degeneration. In spite of these shortcomings, some studies, however, achieved a remarkable degree of "success" as judged from the perspective of today's view of the organization of the visual pathways. Descriptions of direct optic input to the oculomotor nucleus can be repeatedly found in more recent literature ( F R E Y , 1 9 3 7 ; G I L L I L A N , 1 9 4 1 ) .

1.2. Direct retinal connection basale" of Jelgersma

with the "ggl.

opticum

There exists some confusion about the nomenclature of the ggl. opticum basale. As early as 1882 S T I L L I N G followed fibres derived from the marginal bundle of the optic tract towards the rhombencephalon next to the frenulum veli medullaris. These fibres were characterized by him by their medial position and their course dorsally to -the field of termination. It was named the ggl. opticum basale by

BELLONICI

a n d JELGERSMA

(1888),

SINGER

and

MÜNZER

(1890)

(1895).2

1 Some evidence suggests correspondence with commissural fibres on their way to the visceral nuclei of the oculomotor complex via the ncl. of the posterior commissure ( C A R P E N T E R and P I E R S O N , 1973). 2 Later this ggl. was called the ncl. of the medial optic root by P E R L I A (1889), the ggl. isthmi by E D I N G E R and W A L L E N B E R G (1899) and E D I N G E R (1908), the ncl. semilunaris by M E S D A G (1909), and the corpus posticum by G R O E B B E L S (1924). G R O E B B E L S also pointed out that the term ggl. isthmi used by E D I N G E R delineated a nuclear complex different from that described by R A M Ó N Y C A J A L (1911) and A R I É N S K A P P E R S (1921) under the same name. C R A I G I E (1928) and L E G R O S C L A R K (1933a) described the ggl. isthmi as consisting of 3 distinct portions from which only the ncl. tr. isthmo-opticus of their terminology corresponds to the ggl. isthmi of E D I N G E R . A small antero-dorsal part of the isthmo-optic complex was related by these authors with the tr. isthmo-opticus (TIO). The centrifugal character of this optic fibre bundle was questioned as early as 1 8 9 7 by B O Y C E and W A R R I N G T O N , who observed, after lesioning of the superior colliculus (CS) in birds, degenerating fibres and concluded that this bundle contained fibres which degenerate in both the ascending and the descending direction. W A L L E N B E R G ( 1 8 9 9 ) confirmed the centrifugal character of this fibre tract after he succeeded in injuring the ggl. isthmi. He traced degenerated fibres to the opposite optic nerve until they ended in the retina around the cells of the ganglionic layer.

215

This ncl. was long believed to be connected with the retina by the centripetal medial optic bundle ( E D I N G E R and W A L L E N B E R G , 1 8 9 9 ) . M U N Z E R and W I E N E R ( 1 9 0 2 ) and still M A R B U R G ( 1 9 4 2 ) noted the dual organization of retinal fibres reaching the mesencephalon apart from the main trajectory of the optic tract. The dorsal mesencephalic optic ncl. was named ncl. dorsalis nervi optici by M U N Z E R and W I E N E R and ncl. opticus mesencephali dorsalis by M A R B U R G . He dicerned two divisions of this ncl., one medial (ncl. magnocellularis ggl. isthmi) and one lateral portion (ncl. magnocellularis tr. optici), both optic in nature. These "dorsal optic nuclei of the midbrain" (MARBURG) were set against the nucleus opticus mesencephali ventralis, which is represented by the primary end station of retinal fibres in the ncl. ectomamillaris (em) or ventral tegmental optic nucleus (section 1 . 6 . ) . The dorsal fibre component, supplying the isthmic complex (TIO) was consequently termed the dorsal optic (mesencephalic) portion, while the ventral (basal optic root) component was named the ventral optic (mesencephalic) tract. The T P T (section 1 . 5 . ) , was considered as a secondary optic pathway, connecting the ventral optic ncl. with the stratum zonale and opticum of the superior colliculi. Various attempts have been made to homologize the T I O with various other optic fibre bundles (see below). They implicate to mention the T I O and the relationship with a "ggl. opticum basale" which has nothing in common with the following connection.

1.3. Retinal connection to the "ggl. opticum of Meynert (gob.)

basale"

A projection very different to that just mentioned was described by O B E R S T E I N E R ( 1 8 8 7 ) as "basale Opticuswurzel". He was able to trace optic fibres to an area at the lateral border of the tuber cinereum, named "ggl. opticum basale" by M E Y N E R T ( 1 8 7 0 ) . L E N H O S S E K ( 1 8 8 7 ) under this term lumped together three tuberai nuclei, arranged in an oblique mediolateral position (nel. postero-lateralis, ncl. anterior, nel. supraopticus). K Ò L L I K E R ( 1 8 9 6 ) described these nuclei under the erronous inclusion of the ncl. tubero-mamillaris ( = ncl. mamillo-infundibularis, cf. D I E P E N , 1 9 6 2 ) as reaching as far as to the area of the mamillary bodies. He separated the gob proper ( = so) from the so-called nuclei tuberis. The same separation was performed by R A M Ó N Y C A J A L ( 1 9 1 1 ) 1 . According to A R I E N S K A P P E R S ( 1 9 2 1 ) , R E N D A H L (1924)

and

HERRICK

(1925),

EDINGER

(1908,

1911)

seems to have confused the gob with the ncl. ectomamillaris. The usage of "ggl. opticum basale" for the supraoptic ncl. or in homology for the preoptic ncl. of lower vertebrates can be found until recent times. 1 Concerning the nomenclature of the tuberai nuclei and their relation to the supraoptic ncl. see M A L O N E ( 1 9 1 4 ) ; SPIEGEL

and

ZWEIG

(1917);

LARUELLE

(1937) ; D I E P E N (1962) a n d HAYMAKER e t al.

(1934); (1969).

FREY

216

Mai, J. K .

1.4. Anterior accessory optic tract

(AAOT)

In addition to the direct optic connections to the various so-called basal optic nuclei already mentioned, there exists a third connection ( A A O T ) to a terminal within the midbrain tegmentum often termed as well the "basal optic ggl." (EDINGER, 1 9 0 5 ; A . KAPPERS, 1921.) or basal optic ncl. (EDINGER, 1 8 9 2 ; WLASSAK, 1 8 9 3 ; FREY, 1937).

This nucleus has nothing to do with the nuclei bearing the same names discussed formerly. Various other names may be found in the literature 1 . The optic afferent fibres reaching this nucleus are first distinguishable in the posterior chiasmatic area, where all fibres are said to cross the midline. These fibres, in mammals, emerge at least partly through the posterior and dorsal part of the optic chiasma and form the so-called "late-crossing" (HAYHOW) optic axons ("X" of this paper). The trajectory of these fibres and the typical wedgeshaped appearance in transversal sectioned material was already described by BELLONICI (1888) in all vertebrate classes. This intimate relationship between the AAOTfibres and their terminal ncl. (TN) and the suprachiasmatic neuropil in fishes (see p. 219) has led EBBESSON (1968 a) to suggest that the neuropil of the TN of these fibres may be related to the chiasmatic nucleus. Furtheron the AAOT-fibres continue in a caudal direction intermingled with the fibres of the supraoptic commissures and are to be followed in either a superficial or deep position before their termination in the ncl. just mentioned in front of the emerging oculomotor fibres near the substantia nigra (SN), medial to the cerebral peduncle and lateral to the mamillary bodies, with which the ectomamillary ncl. has no relationship. The course of the AAOTfibres is consistently reported in the ventral position within the basal diencephalon. Conflicting results, however, exist about the exact topographical position and the terminal nuclei. These studies, therefore, stand in contrast to the descriptions of a "pupillary pathway", marked by a variable fibre arrangement but an uniform point of termination. The morphological analysis and functional interpretation which FREY developed for the basal optic root (— AAOT) demonstrates the degree of overlap of both the pupillary reflex fibres and the AAOT by 1 Ggl. ovoide seu peduncularis (BELLONICI, 1883, 1888); ggl. ectomamillare (EDINGER, 1889); ncl. ventralis nervi optici ( S I N G E R and M U N Z E R , 1889); nidulus inferius (TURNER, 1891); ggl. tegmenti p r o f u n d u m mediale ( E D I N G E R , cf. M A R B U R G , 1903b); ncl. of the basal optic root (CAIRNEY, 1926); ncl. opticus tegmenti (TSAI, 1925); medial terminal nucleus (HAYHOW, 1959), centrum opticum accessorium ( P E Y R I C H O U X et al., 1977).

application of either morphological or functional criteria. According to most accounts, the fibres were observed swinging superficially around the tuber cinerum and the cerebral peduncle. But there exist other reports stating that the AAOT-fibres2 could be traced superficially up to the lateral part of the cerebral peduncles where all or part of the accessory fibres penetrated the CC in isolated bundles towards the subthalamic ncl. The latter nucleus was already described as receiving optic fibres by STILLING (1878, 1882). Some other authors reported the first as well as the latter trajectory (NIIMI et al. 1961). Another variation in the course of the anterior accessory optic fibre system was recognized by LASHLEY (1934) and PACKER (1941). These authors identified fibres which leave the characteristic position in the basal hypothalamus but finally rejoin the optic tract or the PAOT ("§" in table). Among mammals studied so far, the AAOT (or basal optic root) distinguishable as separate morphological entity — not rejoining the main optic pathway — could be identified in the characteristic anatomical position with termination in the medial terminal ncl. in only marsupials, lagomorphs and rodentia. In other orders the existence of the AAOT is still questioned and has not yet been demonstrated in primates. By means of ARG this bundle has hitherto only been demonstrated in the albino rat (MAI, 1976) a n d i n t h e o p o s s u m (LENT e t al., 1976).

1.5. Tr. peduncularis transversus (TPT) accessory optic tract (PAOT)

and posterior

It was v. GUDDEN, who in 1870 and in more detail in 1881 gave the first substantial accounts of a fibre bundle called by him the tr. peduncularis transversus 2 Like the terminal ncl. of AAOT-fibres within the ventral midbrain tegmentum, also t h e bundle itself was given various names: Radix Luysiana ( S T I L L I N G , 1 8 7 8 ) ; peduncular fibres ( B E L L O N I C I , 1 8 8 8 ) ; basal optic root ( E D I N G E R , 1892); Tr. commissurae postchiasmaticae ad ggl. ectomamillare ( G A U P P , 1 8 9 7 ) ; ventral medial optic bundle ( M U N Z E R and W I E N E R , 1 9 0 2 ) ; radix basalis optica ( G O L D S T E I N , 1 9 0 5 ) ; anterior accessory optic fascicle ( B O C H E N E K , 1 9 0 8 ) ; basal bundle of optic tract ( H E R R I C K , 1 9 1 7 ) ; anterior accessory optic tract ( T S A I , 1 9 2 5 ) ; tr. opticus accessorius rostralis ( C L A R A , 1 9 5 9 ) ; inferior fasciculus of t h e accessory optic system ( H A Y H O W , 1 9 5 9 ) ; mesencephalic optic tract ( P E R N K O P F , 1 9 5 7 ) ; ventral diencephalic bundle ( G I O L L I , 1 9 6 5 ) ; tract of the ectomamillary ncl. (quoted according to E B B E S S O N and R A M S E Y , 1 9 6 8 ) ; Fa.sc. ventralis systematis optici accessorii ( C U M M I N G S and L A H U N T A , 1 9 6 9 ) (see table).

Accessory Optic and R e t i n o - H y p o t h a l a m i c S y s t e m

(transpeduncular tract). This tract was distinguished first from the anterior margin of the superior colliculus, passing then ventro-laterally along the ventral part of the medial geniculate body towards the base of the brain. It was easily distinguished crossing the lateral margin of the cerebral peduncle where it commonly penetrated but could be easily traced towards the point of termination at the exit of the oculomotor fibres. There, the fibres were lost forming a nuclear-like matter in the angle between the mamillary body and the peduncular margin in the midbrain tegmentum, stretching dorso-laterally until the area between the ventral rim of the red nucleus and the substantia nigra. In his classical experiment, after performing unilateral enucleation of the newborn rabbit, v. G U D D E N demonstrated that the transpeduncular fibres of the contralateral side underwent degeneration. He had, however, not been able to make any definite conclusions concerning origin and termination of the transpeduncular tract fibres. He denied an origin within the superior colliculi because this tract did not exhibit any alterations after destruction of the colliculi. Although the results of v. G U D D E N rested on macroscopical analysis, he already was able to describe the basic arrangement of fibres as proceeding basalward along the superficial tegmentum and obliquely to the peduncular fibres. In spite of the irregularities of fibre distribution within the same species and among different orders, already mentioned by v. GUDDEN, subsequent authors have supported his investigations and findings of the transpeduncular tract. Only some investigators reported nonsuperficial coursing fibres (MÜNZER and W I E N E R , 1902;

CAMPBELL

et

al.,

1967;

GIOLLI

and

Concerning the origin and the quality of fibres there existed diverging opinions. Supporting evidence to v. G U D D E N ' S observation, that the integrity of the T P T was dependent on the retina was given by the rudimentary character or even absence of this bundle in amblyopic animals already mentioned by v. G U D D E N ( 1 8 7 0 ) and confirmed by F R A N K L HOCHWART ( 1 9 0 2 ) a n d L U N D a n d L U N D ( 1 9 6 5 ) .

The

localization of the cells of origin within the eye — by no means generally accepted (KOLLIKER, 1896; TÜMIANZEW, 1 8 9 8 ) — was established by S I N G E R a n d M Ü N Z E R ( 1 8 8 9 ) a n d MÜNZER a n d W I E N E R ( 1 9 0 2 ) . TPT

as

described

by

v . GUDDEN,

the term T P T for only that distance, discussed below, among them: the composite nature of the T P T and the possibility of synaptic interruption between PAOT and TPT-fibres. Reference has already been made (section 1.1.) to the opinion that the T P T is mediating pupillary fibres ( S C H W A L B E , 1 8 7 9 ; P E R L I A , 1 8 8 9 ; E D I N G E R , 1911).

who ascribed, as earlier did M A S part of the TPT-fibres belonging to the ciliary nerves, traced these fibres together with the oculomotor root to the oculomotor nuclei. He stressed the differences in the development of the T P T and regarded the "transpeduncular ganglion" as part of the ciliary ggl. that has failed to move orbitally. B E R N H E I M E R (1899) as later T S A I (1925) and H A MASAKI and MARG (1960b) formulated the widely accepted opinion, that the T P T has no direct connection with the oculomotor nuclei and exerts no direct influences upon the ciliary muscles. S I N G E R and M U N Z E R (1889) and MUNZER and W I E N E R (1902) were able to demonstrate the termination of the TPTfibres within a circumscribed nuclear mass, called "ncl. ventralis nervi optici". They tentatively homologized this ncl. with the ncl. peduncularis, designated by B E L L O N I C I (1888). In amphibians ( G A U P P , 1896, 1899), in reptiles (EDINGER, 1899), in birds ( B O Y C E and WARRINGTON, 1899), in fishes ( G O L D EDINGER (1911)

SAUT ( 1 8 9 6 ) ,

STEIN,

1905)

and

in

mammals

(MARBURG,

1903)

this nucleus was called "ggl. ectomamillare" "ncl. ectomamillaris".

1.6.

Arrangement

and

interconnections

of

or

AOS-fibres:

CREEL,

1973).

The

217

represents

therefore only the distal mesencephalic section of a fibre tract originating in the eye. Nevertheless, it came into use, to describe the whole pathway as PAOT (or related nomina) and only the distal part of that pathway according to the historical description as TPT. There exist other reasons to reserve

The fact that the terminal nucleus of the T P T of higher mammals occupies the same position at the medio-basal midbrain tegmentum as the ncl. ectomamillaris of lower vertebrates and that both nuclei share some histological characteristics, induced MARBURG ( 1 9 0 3 ) , WALLENBERG ( 1 9 0 4 ) , LOEPP ( 1 9 1 2 ) ,

and H I R A I W A ( 1 9 1 5 ) and finally G I O L L I to homologize the T P T and its corresponding terminal nucleus in several vertebrates with the basal optic root and the related terminal nucleus, the ncl. ectomamillaris of lower vertebrates. B O C H E N E K ( 1 9 0 8 ) confronted this hypothesis in demonstrating the existence of two "accessory" optic fibre paths in the rabbit. These were the T P T and a ventral bundle, called the " F c . accessorius opticus anterior". The degenerated fibres were traced by B O C H E N E K to two different nuclei: to the subthalamic ncl. from the accessory optic bundle and to the ggl. ectomamillare from the TPT. The latter could be traced in the same position as the T P T KOSAKA (1965)

2:1.8

Mai, J . K .

described by (1.889),

SINGER

PAVLOV

and

MUNZER

(1900), B E R L

(1889);

(1902);

PERLIA

WALLENBERG

( 1 9 0 4 ) , and VAN GEHUCHTEN ( 1 9 0 6 ) . In his attempt to correlate his accessory fascicle and the TPT with the accessory optic bundles of lower vertebrates he related the anterior accessory optic bundle and the caudal part of the subthalamic ncl. with the basal optic root and the ggl. ectomamillare. The TPT was esteemed by him as homologous with the tr. optici ad ggl. isthmi. He explained the difference in the position of the ggl. isthmi and the ggl. of the TPT by the developmental increase in the volume of the inferior colliculi of mammals. T S A I ( 1 9 2 5 ) confirmed the dual organization of the AOS in mammals set against as AAOT and PAOT. He also reported the separate termination of both bundles. The anterior bundle was alleged to ramify within the sut, whereas the posterior bundle was identified as terminating within the "ncl. opticus tegmenti". As homologous with the AAOT a basal optic bundle was described later by F R E Y ( 1 9 3 7 ) in all vertebrate classes. As the most consistent feature of this bundle in all animals studied, F R E Y alleged the constant position at the basal surface of the hypothalamus and the orientation towards the oculomotor nuclei with which he still suggested the ncl. of the basal optic root has a direct fibre connection. Comparative embryological studies led him to believe that the basal optic root serves as a part of a reflex arc mediating parasympathetic influences to the oculomotor nuclei. Finally H A Y H O W and coworkers ( 1 9 5 9 — 1 9 6 6 ) reported a different course of the AAOT and PAOT — fibres, which, however, terminated within the same nucleus, (the "medial terminal nucleus" in their terminology). The duplicate arrangement of the AOS-fibres in mammals — expressed by a ventral component of horizontally directed fibres and a dorsaly oriented component — separating at different levels from the optic tract but ending in the same nucleus in the basal midbrain tegmentum has not been established in non-mammalian vertebrates. Nevertheless, various attempts have been made to homologize the basal optic root of lower vertebrates with either the T P T ( M A R B U R G , 1 9 0 3 ) , the A A O T (BOCHENEK, 1 9 0 8 ; F R E Y ,

1937) or the P A O T

(GIL-

LILAN, 1 9 4 1 ; G I O L L I , 1 9 6 5 ; K N A P P a n d K A N G , 1 9 6 8 ) . 1

There exist no conclusive reasons to establish concepts of homologizing the various parts of the AOS in different vertebrates ( E B B E S S O N and R A M S E Y , 1 A b o u t a t t e m p t s t o homologize t h e T I O and t h e T P T see page 2 1 5 ; a b o u t homologies between t h e A A O T and t h e R H S see page 224.

1968), until either the homo- or the heterogeneity of the various components is demonstrated by ontogenetic, functional or comparative phenomena. Still another problem arises, since V O N E I D A and S L I G A R (1976) have described the "accessory optic ncl." as well as the "ectomamillary ncl." in the same species (Astyanax mexicanus). Without any comment from the authors, it remains unclear whether these names are refered to two terminal areas with different properties or whether they intended to establish new homologies. Furthermore, H A Y H O W and coworkers (1959 to 1966) showed that the AOS-fibres had topographical relationship with not only the medial terminal ncl. By using the N A U T A - G Y G A X technique they were able to delimitate other accessory optic termination sites, which has been repeatedly alledged since A D E L H E I M (1867), TÜMIANZEW (1898) and R E T Z I U S (1898) in normal and experimental material first reported the presence of an additional nuclear group at the antero-lateral margin of the superior colliculus, believed to be intimately related with the TPT. According to their description, this nucleus should be regarded as the analogue of the dorsal terminal ncl. of H A Y H O W . Later, reports about diffuse or circumscribed agglomerations of cells within the trajectory of the TPT were quite numerous, but not until H A Y H O W and coworkers these groups were systematically defined as the dorsal, lateral and the medial terminal nuclei. The dorsal terminal ncl. (dt) located at the anteriorlateral margin of the CS, medial to the BCS and immediately in the groove between the BCS and the superior pole of the cgm, shows intimate morphological and functional relationship with the pretectal nuclei. It is rather small and can be seen in only a few sections. In the horse, this ncl. was described located nonsuperficially, medial to the caudal portion of the cgm in close proximity to the caudal and suprageniculate pretectal nuclei (CUMMINGS and LAHUNTA, 1969). The lateral terminal ncl. (It) is found immediately superior to the dorso-lateral edge of the CC and stands in close relation to the lower pole of the cgm. It consists of a large band of cells beginning at the ventrolateral surface of the CC. As it passes caudally, it shifts in lateral direction over the surface of the CC. In caudal sections the It is located at the medioventral pole of the cgm. The portion of the It located on the cerebral peduncle is rather thin and contains only few cells ( = "peduncular extension" in the terminology of T I G G E S and T I G G E S , 1969a). The cells composing the It can hardly be separated from the cglv and the ZI of the subthalamus. The It, like the

Accessory Optic and R e t i n o - H y p o t h a l a m i c S y s t e m

dt is traversed by numerous blackened fibres after enucleation

of t h e

opposite

eye

(HAYHOW a n d

co-

workers, 1.959-1966). The medial terminal ncl. (mt) corresponds topographically and cytoarchitectonically to the above mentioned TN of the AAOT and PAOT, respectively. The position of the mt has mostly described to be at the level of the outgoing oculomotor root, within the limits of the tegmentum, but there seem to exist some variations within different vertebrate classes. In some amphibians the mt is represented only by neuropil (SHANKLIN, 1933; Riss et al., 1963). In Amblystoma, it was observed by H E R R I C K ( 1 9 2 5 ) embedded within the motor tegmentum. In birds, the ncl. is located more rostrally. According to R E N D A H L ( 1 9 2 4 ) it extends through the whole synencephalon. It has been classified in birds as thalamic ncl. by H U B E R and C R O S B Y ( 1 9 2 9 ) , as synencephalic ncl. by RENDAI-IL ( 1 9 2 4 ) , and as partly mesencephalic and partly diencephalic ncl. by P A L M GREN ( 1 9 2 1 ) .

The delineation and description of this ncl. as far anterior as the lateral ventricular area next to the C O in fishes ( G O L D S T E I N , 1 9 0 5 ; HOLMGREN, 1 9 2 0 ) and

reptiles

(EDINGER,

1899)

seems

to

be

due

to

confusion with other nuclei. In reptiles the cells are comparative large stellate, round or oval (SHANKLIN, 1933); in birds, a mixed population of large, scattered cells together with smaler ones are to be found. With the exeption of some higher primates (Galago, Saimiri, Aotes, H A S S L E R , 1 9 6 6 , see also p. 2 2 2 ) , the mt of mammals has a triangular shape with the base at the superficial ventral tegmentum just anterior to the attachement of the oculomotor nerve and medial to the cerebral peduncle. It ascends dorsolaterally to the midbrain reticular formation, surrounded by the substantia nigra and the zona incerta. The oblique perpendicular extension induced F R E Y ( 1 9 3 7 ) to conclude that the TPT-fibres coursing between the cells of the mt establish a secondary connection of the basal optic root. Due to the slightly curved shape of the dorsal extension of the mt this part may appear separated from the base of the nucleus, especially in sagittal sections. This appearance has erronously induced descriptions of two different, incoherent portions of the nucleus. Some authors divided the mt into ventral and dorsal divisions ("d" and " v " of table) on the basis of phylogenetic properties ( W A L L E N B E R G , 1 9 0 4 ) or cellular differences (GIOLLI e t a l . , 1 9 6 8 ; CUMMINGS a n d LAHUNTA,

1969;

of this nucleus. In fact, the cellular composition of the mt of different species differs so stikingly by the number, size, shape and arrangement of the cells, respectively, (GILLILAN, 1941; YAMADA, 1 9 7 4 )

219

et al., 1943) that more comparative studies are needed to give substantial support to this separation. H A Y H O W and coworkers, who gave the first classification of the terminal nuclei of the AOS, traced the accessory fibres not as separate bundles, but as more or less isolated prominent portions of a broad, very thin fibre system. The individual fibre groups may thereby only arbitrarily be classified. Consequently, H A Y H O W et al. did only describe divisions of a so-called AOS with different predominance in supplying the dorsal, lateral or medial terminal nuclei thereby covering great areas of the di- and mesencephalic lateral and ventral surface, basal to the main optic projection. This observation was first mentioned by S T I L L I N G , who in 1882 delineated what he called the "radix descendens nervi optici", consisting of 2 bundles of different size separating one after the other from the main optic tract and coating the whole lateral and basal surface of the di- and mesencephalon. Different portions of the superior component (SF) leave the optic tract at the ventral, lateral and dorsal plane. The classical T P T of v. GUDDEN, emerging from the BCS corresponds to the posterior part of the superior fasciculus (SF). This schema of H A Y H O W et al. has been adopted in the present study. The various descriptions of the superior component — for practical reasons referred to as the PAOT — are therefore (furtheron) marked as either (a), (m) or (p), respectively. This means, that PAOT-fibres leave the optic tract near the ventral part of the CC ( = a), or before the T i l reaches the cgl ( = m) or next to the BCS ( = p). The description of the AOS of H A Y H O W et al., although related to only some mammalian species, has been immensely fruitful and has been adopted schematically as the framework for the use as a generalized model with which to compare individual spezies. In mammals, their schema is now generally accepted and has undergone only slight modifications ( G I O L L I , 1965; T I G G E S andTiGGES, :1969b; K O S T O V I C , 1971; MAI, 1976). These variations are incongruous only in the assessment of the innervation of the various TN or in the incorporation of more or less than the three terminal nuclei. According to their proposal, the AOS (of mammals) consists of two sets of fibres (the AAOT and the PAOT), which ordinarily may not be separated as distinct bundles before they reach the terminal nuclei. Various parts of these fibres are well or nondeveloped in different species: HUBER

The AOS of primitive mammals bears some features in common to the organization of the AOS in

Mai, J . K.

220

non-mammalian vertebrates (GIOLLI, 1965). In the rodents, the AOS and the medial terminal nucleus reaches the peak of development (GILLILAN, 1941; H U B E R et al., 1943). In phyletically more advanced animals a true reduction of the AOS occurred. Recent studies in carnivora provide some evidence that the inferior fasciculus of the AOS is lacking (THORPE and HERBERT, 1976). Among primates, especially the medial terminal ncl. seems affected ( W A L L E N B E R G , 1904;

GILLILAN,

1969;

CAMPOS-ORTEGA

ORTEGA

and

1941;

CLUVER,

GIOLLI, and 1968;

1963;

GLEES,

CAMPBELL,

1967;

TIGGES

and

CAMPOSTIGGES,

1968, 1969a, b ; H E N D R I C K S O N et al., 1970; T I G G E S and O'STEEN, 1974). Functional considerations have to be aware of the morphological reductions of the inferior fasciculus and the medial terminal ncl. Conclusions regarding the organization of the AOS have to be drawn with some reservation, since most results were obtained after the application of silver impregnation techniques for tracing degenerated fibres. These methods often fail to impregnate degeneration products within marsupialian (LENT et al., 1976) as well as in primate tissue (TIGGES and O'STEEN, 1974).

On the other side, the lateral terminal nucleus of primates is much larger than in lower mammals (SEHMSDORF, 1969) and seems to have adopted an increase in functional significance. In some ungulates it has been shown that the lateral terminal nucleus is well developed and is represented as an elongated prominence that extents orally over the lateral third of the CC with no detectable fibres emerging from the

It

to

the

mt

CAMPOS-ORTEGA,

(CUMMINGS a n d LAHUNTA,

1969;

1970). In Saimiri, the It consists

of two components

(TIGGES and TIGGES,

1969a),

one at the lateral surface of the CC, and another, described as "peduncular extension" (TIGGES and TIGGES). It has been argued that the peduncular portion in ungulates and higher primates represents the medial component of the general mammalian plan. This means that the mt migrated during evolution from its position medial to the CC to the position on the latero-ventral surface, and became partially incorporated into the It, whereas the small perpendicular fibre groups would represent the AAOT (CUMMINGS and LAHUNTA, 1969; S E H M S D O R F , 1969). T I G G E S (1970) questioned this hypothesis by the finding that in squirrels, which are not closely related to primates, there is a peduncular extension of the It in addition to a well developed mt. Possibly, the higher functional role of the It in the ascending phylogenetic scale is concommittant with an uncrossed portion innervating this ncl. as suggested in several mammals (HAYHOW et al., 1960; CUMMINGS a n d LAHUNTA, 1 9 6 9 ; H E N D R I C K S O N e t a l . ,

1 9 7 0 ; KANAGASUNTHERAM a n d K R I S H N A M U R T I , 1 9 7 1 ; PASIK

and P A S I K , 1971; L I N and INGRAM, 1972b;

PASIK a n d PASIK, 1 9 7 3 ; PASIK et al., 1 9 7 3 ; LIN et al.,

1976).

1.7. Arrangement and interconnections after autoradiographic analysis The autoradiographic analysis of the AOS in the opossum (LENT et al., 1976) and in the albino rat (MAI, 1976) yielded results which appeared to be more complex than observed after application of silver impregnation methods. MAI points out the striking contrast between the very dense label overlying the TN, esp. the mt, and the lightly labelled trajectory of the afferent fibres. With regard to the dense label within even single fibres of the main optic tract, it was concluded that besides the paucity of loosely arranged afferent AOS-fibres the delicate labelling may only be explained by profound differences in the transport capacity of both fibre systems. The AOS as observed by MAI in the rat was composed of only crossed AAOT and PAOT-fibres with both superficially and deep coursing fibres distributed in close relation to the CC. Besides the AOTN, also the sut and the SN have been found labelled. The AAOT was observed emerging at least partially from the late crossing chiasmatic bundle, coursing tangentially to the caudal margin of the sc and intermingling with the fibres of the postoptic commissures. Some fibres were then followed piercing the peduncular fibres and proceeding through the subthalamic neuropil towards the dorsal part of the mt (Fig. 1). The subthalamic nucleus, according to the elevation of the number of SG, seemed to receive synaptic contact by this bundle. The other AAOT-fibres were followed along the basal surface

Pf

""

pf

Fig. 1. Proposed model of the distribution of accessory optic fibres as abserved in rodents (1: dt; 2: It; 3: mt; for further explanation see text).

Accessory Optic and Retino-Hypothalamic System

of the hypothalamus disappearing in the ventralmost limit of the mt. The occurence of fibres piercing the CC and ramifying within the sut have been repeatedly observed

221

YAMADA, 1974). The functional relationship between both nuclei is demonstrated by the distribution of dopaminergic cells giving rise to the striato-mgral (UNGERSTEDT, 1 9 7 1 , SHIMADA e t a l . , 1 9 7 6 ) , a s well a s

r a b b i t (BOCHENEK, 1 9 0 8 ; LOEPP, 1 9 1 2 ; KOSAKA a n d

by the extensive overlap of dendritic fields in the pars compacta of SN with neurons originating in the ventral tegmental area, observed in Golgi studies

HIRAIWA,

in the rat (JURASKA et al., 1977). W i t h regard to the

i n r a t (CHANG, 1 9 3 6 ; GILLILAN, 1 9 4 1 ; HAYHOW e t al., 1960;

SOUSA-PINTO 1915;

and

CASTRO-CORREIA,

OVERBOSCH,

1.927;

1970),

FREY,

1937;

HANDA, 1 9 5 1 ; NIIMI e t a l . , 1 9 6 1 ; BAN e t a l . , 1 9 6 5 ) ,

results

in both animals (KOELLIKER, 1896) and in man

GRAYBIEL (1974) after injecting tritiated amino acids into the cglv of the cat, it may be assumed that the delineation of the deep PAOT projection may be engendered by transneuronally transported label, because the efferent fibres of the cglv take the same distribution in the ventral midbrain tegmentum. This projection was, however, observed after application of 3H-leucine, known to be transneuronally transported in only very limited amounts. This precursor is therefore unsuited to label secondary fibre pathways. Secondly, the projection could be seen even after short survival time, where labelling of the visual cortex of the experimental animals was virtually not detectable. Finally, other more pronounced secondary projections which were disclosed after injections of isotopes in subcortical visual nuclei were not found labelled in those animals. Reflecting the autoradiographic results it seems rather evident that the projection described by LIN and INGRAM (1972) after unilateral enucleation in cats as a so-called "anterior component of the AOS", piercing both the CC and the reticular complex of the thalamus and travelling along the dorsal edge of the cerebral peduncle may be due to misinterpretation either of the deep PAOT fibres or of the fibres emerging from the cglv. It seems now to be evident, that the A AOT and PAOT are parts of an interconnected system. Only the main structures, where synaptic transmission takes place, are hitherto fully established. I t may be that there exist still other continuations of AOS-fibres. The direct connection with various limbic structures has repeatedly been reported. GILLILAN (1941) followed accessory optic fibres through the supramamillary commissure, regarded,

(MIRTO, 1 8 9 6 ) .

Collaterals derived from AOT axons projecting to the mt were observed in the sut (NIIMI et al., 1961; BAN e t a l . , 1 9 6 5 ) a n d i n t h e S N (BAN e t a l . , 1 9 6 5 ) . HAYHOW e t al.

(1960)

a n d GIOLLI

(1961)

followed

optic axons through the sut but were not able to observe any synaptic relationship within that ncl. They discerned only axonal degeneration of fibres passing to the mt (d). The superficial PAOT-fibres appeared distributed corresponding to the description of HAYHOW et al. Additionally, however, a projection, was seen emerging from the internuclear plexus betneen the dorsal and ventral lateral geniculate bodies. This area was separated from the cglv by HAYHOW et al. (1960, 1962) for its intimate relation to the AOS as the lateral terminal nucleus. The authors stressed the difficulty in delineating this area from the cglv, the ZI and the subthalamic nucleus, especially at the anterior pole. They also showed that the posterior part of this cellular aggregate is arranged like a delicate lamina of only a few cells. This cellular material has been demonstrated to be clearly labelled after intraocular injection of tritiated amino acids by H I C K E Y a n d SPEAR ( 1 9 7 6 ) a n d MAI ( 1 9 7 6 ) i n r a t s .

The former authors have described this medioventrally directed labelled zone as "intergeniculate leaflet", extending towards the external division of the cglv and finally merging with the zona incerta. MAI was able to establish the further trajectory of this intergeniculate leaflet-projection to the substantia nigra and the medial terminal nucleus. He also established the relationship with the It. The projection from the intergeniculate leaflet appears relatively minor; indeed, only a slight, but continuous elevation of SG gave evidence of that connection, carrying direct impulses to the dopaminergic nigral and adjacent tegmental area. In this context it is worth mentioning that PALMGREN (1921) assumed that the mt in lower vertebrates originates from the same neuropil as the SN. In mammals, the similarities or homologies of the cellular populations of the SN and the mt were

obtained

by

EDWARDS

et

b y GURDIJAN ( 1 9 2 7 ) a s l i m b i c i n

al.

(1974)

nature.

and

GERGEN

repeatedly reported (KOSAKA and HIRAIWA, 1 9 1 5 ;

and MACLEAN, (1964) after flash-light and electrical stimulation of squirrel monkeys had suggested, the visual system utilizes limbic pathways to influence neural activities in the hypothalamus. As pathways mediating these influences they assumed a totally crossed, "labile" multisynaptic system. As parts of this they alleged the PAOT, the medial terminal ncl., the mamillary peduncle and the anterior thala-

CASTALDI, 1 9 2 3 ; GIOLLI, 1 9 6 1 ; GIOLLI e t a l . ,

m i c n c l . T h e o b s e r v a t i o n b y CUMMINGS a n d LAHUNTA

Hirnfor'chimg, Bd. 19, Heft 3

1968;

16

222

Mai, J. K.

(1.976) that direct optic fibres in the horse take a mesad continuation from the medial terminal ncl., fits to that proposed pathway. MAI (1976) observed increased numbers of SG towards the decussatio supramamillaris. This projection was distinct from the AAOT-fibres, which at this position take a superficial arrangement, by the fountainous-like assortment from the medial terminal ncl. and by traversing loosely grouped in dorso-medial direction. This finding may support that some fibres continue to the decussatio supramamillaris. According to observations of GILLILAN, obtained from non-experimental material, fibres from the ventral part of the decussatio supramamillaris are linked with the fornix. The functional significance of direct retino-limbic relationship w a s discussed b y CONRAD a n d STUMPF

(1975) who, using light microscopic ARG after intraocular injection of mixtures of tritiated A As in Tupaia reported a very dense labelled area, alleged by the authors as anterior thalamic ncl.

terminals within the terminal nuclei was suggested f r o m t h e studies of BAN et al. (1965) in MARCHI series of enucleated r a b b i t brains, of ABPLANALP (1974)

after partial retinal lesioning in sciurids and of KOSTOVIC (1971) i n F I N K - H E I M E R a n d NAUTA p r e p a -

rations of rat brains. Similar conclusions were drawn from the presence of large receptive fields of mtunits after electrophysiological recording (WALLEY, 1967).

The observations favoring a diffuse arrangement of AOS-fibres are not as convincing to gain evidence against the principle of retinotopic organization within t h e p r i m a r y optic system (see GIOLI.I a n d POPE,

1971). With all the reservation which is needed in the interpretation of light microscopical findings without selective lesioning of different retinal areas, results o b t a i n e d b y HAYI-IOW et al.

(1959—1966)

using the NAUTA-GYGAX technique and by MAI (1976) employing ARG, speak in favor of a separation of the AOS-fibres within the optic chiasm. There, the AAOT-fibres can be followed in the mediodorsal part as late crossing retinal axons which deviate from the main optic tract at the medial edge 1.8. Topic organization of the 40S fibres: of the CC in the lateral hypothalamus. Concerning the distribution of PAOT fibres no For evaluation of the function of the AOS it would • be important to ascertain, whether or not the acces- reports are available exept the observation of HAsory optic pathways are topographically, i.e. retino- MASAKI a n d MARG (1960 b), m a d e b y physiological topically organized. Unfortunately, this question studies on the AOS of rabbits, that the AOT-fibres did not traverse the cgl. is by no means elucidated, in spite of the work of Considerable interest would also attend an experiL E GROS CLARK ( 1 9 4 2 ) , BODIAN ( 1 9 3 7 ) , GAREY a n d mental resolution of the question, as to whether the POWELL (1968) a n d o t h e r s . AOS fibres bifurcate before supplying the various BROUWER a n d coworkers (1923, 1926) r e p o r t e d degenerated AAOT-fibres after lesioning the ventral terminal nuclei. As far as we are concerned, no conhalf of the retina and the degeneration of the T P T clusive electrophysiological studies exist to test the after destruction of the ventrolateral retina! quad- occurrence of bifurcated fibres. Morphological obrant. LASHLEY (1934) stated that the AAOT-fibres servations on this problem, again, are obtained from originating within the upper temporal quadrants s t u d i e s of HAYHOW (1959) a n d of HAYI-IOW e t a l . and the PAOT-fibres stemming from the temporal (1960) who state that the degenerating terminals quadrants outnumber the remaining accessory fibres. within the AOTN were derived from collaterals of both the ascending and descending accessory optic A l s o LATIES a n d SPRAGUE ( 1 9 6 6 ) , u s i n g t h e NAUTAtechnique, presented evidence in the cat for the tract "reflex collicular fibres". Their findings were supported by GIOLLI and GUTHmain origin of AOS-fibres within the temporal retinal quadrants. GIOLLI (1963) noted that the accessory RIE (1969) a n d HOLBROOK a n d SHAPIRO ( 1 9 7 4 ) . I n optic fibre diameter in Macaca monkeys is as small this context, it is interesting that in Talpa, where a as that of the fibres from the fovea centralis and connection between retina and CS is lacking, there suggested that the AOT-fibres originate from the i s n o e v i d e n c e of a A O S (LUND a n d LUND, 1 9 6 5 ) . Electrophysiological data obtained on the AOS fovea, and, since they decussate in the chiasma, from the nasal half of the fovea. This point of origin fits are rather conflicting. A classification of AOS-fibres with the results obtained by LAZAR (1973) after based on conduction velocity and threshold is not retinal stimulation for release of optokinetik nystag- y e t a c c o m p l i s h e d . HAMASAKI a n d MARG (1960) a n d mus in frogs after destruction of the AOS. From his MARG (1973) s t u d y i n g t h e AOS in r a b b i t a n d m o n findings it could be supposed that the AOS fibres key could not obtain antidromic response from the contralateral optic nerve after electrical stimulation originate from the nasal retina. The diffuse origin of AOS fibres within the retina of the transpeduncular ncl. (tpt = mt). They conand the diffuse distribution of the accessory optic cluded that a synaptic relay station exists between

Accessory Optic and Retino-Hypothalamic System

the transpeduncular ncl. and the optic nerve. Additionally, the effect of post-tetanic potentiation, effects of asphyxia on synaptic transmission and maximum frequency limitation of the response, forced them to suggest a polarized pathway. Consequently, they had to postulate that the AAOT, despite of its established morphology, acts without functional significance. H I L L and MARG ( 1 9 6 3 ) on the other side, stated the retinal origin of evoked potentials within the tpt. The latency distribution of the tpt after monochromatic stimulation of the rabbit's retina led them to conclude that the origin was not in the accessory pathway or the It (the ncl. of the PAOT in their terminology). The technique applied for the tracing of axon destinations by antidromic activation seems inadequate to permit precisely a determination of the spatial location of the structure involved in photic response of the AOS. This is due to limited accuracy, because an axon can be activated at some distance from a stimulating electrode and at any point along its lenght. Nervertheless the results presented by HAMASAKI and MARG ( 1 9 6 0 ) and of MARG ( 1 9 7 3 ) are in accordance with the findings in primates obtained by G I O L L I ( 1 9 6 3 ) using silver impregnation techniques of degenerated fibres.

STILLING, 1 8 8 2 ; BRAUTH a n d K A R T E N , 1 9 7 7 )

223

or

in-

directly via the inferior olive and the climbing fibres (MAEKAWA a n d SIMPSON, 1 9 7 2 ; I T O e t a l . , 1 9 7 4 ; I T O a n d M I J I S H I T A , 1 9 7 5 ; T A K E D A a n d MAEKAWA,

1976).

The other role is associated with possible influences of morphine on endocrine function. It has been observed in the rat, that all accessory optic structures are enriched with opiate receptors. Unilateral enucleation was followed by contralateral depletion of opiate receptor grains (see S N Y D E R and SIMANTOV, 1977).

2. Retinohypothalamic system (RHS) 2.1.

Background

Besides the portion of the optic system which is responsible for the complex psycho-physiological phenomenon of vision, for the autonomic reflex mechanisms, and for midbrain interactions mediated by the AOS, there exist numerous biological, experimental and clinical observations speaking in favour of influences of light on diencephalic vegetative centres thus regulating neuro-endocrine processes (see HAGUE,

1964;

HOLLWICH,

1964;

MOLLENDORF

a n d BARGMANN, 1 9 6 4 ; S C H A R R E R , 1 9 6 4 ; S O L L B E R G E R , 1965;

BUNNING,

1967;

v . MAYERSBACH,

1967;

BE-

NOIT a n d ASSENMACHER, 1 9 7 0 ; HOLLWICH a n d D I E K -

1.9. Connections of the AOTN

Environmental light plays that importent part in regulating neuroendocrine functions by virtue of its daily variations and synchronizes circadian rhythm (see A N D R E W S and HUES, 1 9 7 2 ; W U R T M A N , 1 9 7 5 ) .

I t is an uncontradicted observation of all authors applying degeneration techniques and studying the AOS after the reasonably long survival times that undegenerated fibres within the accessory pathway may be observed. The composite nature of the accessory optic tracts is also evident after destruction of the AOTN ( G I O L L I , 1 9 6 1 ) . Electron microscopical studies of t h e It (PASIK et al., 1 9 7 0 , 1 9 7 1 , 1 9 7 3 ) a n d of t h e m t (LENN,

1972;

TIGGES a n d TIGGES,

1972;

YAMADA,

1974) after uni- or bilateral enucleation revealed that only a relatively small percentage of synaptic terminals underwent degeneration. GOLGI study of the mt in the rabbit demonstrated the existence of diverse nonaccessory optic input and efferent projections of this nucleus ( G I O L L I et al., 1 9 6 8 ) . The origin of other afferents than the accessory optic as well as secondary connections are listed in the table and will be discussed on the basis of other studies (see also: W E L L S and SUTIN, 1 9 6 3 ;

GIOLLI e t al., 1 9 6 8 ; PASIK a n d PASIK,

1 9 7 1 ; C A R P E N T E R a n d P I E R S O N , 1 9 7 3 ; TROIANO a n d SIEGEL, 1975, 1976).

Special attention may thereby directed to two very different roles played by the AOS. One is associated with the control of the vestibular ocular reflex, mediated either by direct efferent fibres (cf.

FOLK, 1 9 7 3 ;

F A R N E R e t a l . , 1 9 7 3 ; SCHEVING e t

al.,

1 9 7 3 ) . Actions of light may not be necessarily or exclusively mediated via the retinal ganglionic cells and the optic system but may interfere directly on light sensitive brain tissue. The existence of extraretinal photoreceptors ( E R P ) is repeatedly reported in non-mammalian vertebrates. The E R P s are involved in either the entrainment of some circadian rhythms or the photoperiodic induction of testicular recrudescence (see T I E N HOVEN and PLANCK, 1 9 7 3 ) . In mammals, however, the existence of extraretinal light perception has not been convincingly demonstrated despite some reports ( L I S K and K A N N W I S C H E R , 1 9 6 4 ; Z W E I G et al., 1 9 6 6 ) . Neither has it been possible to demonstrate the effects of environmental light in blinded mammals on endocrine function nor has there been observed delay in maturation of neurosecretory function by changing light exposure or blinding. Therefore, distinct pathways between the retina and the hypothalamus have been postulated as possible information channels mediating light sti16*

224

Mai, J. K.

muli to the photodynamically responding hypothalamic neurons either directly or via one of several centres integrating ex- and intrinsic information and exerting control of the rhythmicity of light-depending autonomic function. This hypothetical system has been described by various terms: "energetischer Anteil der Sehbahn" (HOLLWICH, 1 9 5 2 ) ; "vegetative optische Wurzel" (KNOCHE, 1956—1960); "photo- or opto-sexual reflex" ( B E N O I T and ASSENMACHER, 1 9 5 9 ) , "optovegetative Reflexbahn" ( O K S C H E , 1 9 6 0 ) . Despite much research, the trajectories remained obscure until recent time and there still exist many contradictory results. This résumé is quite surprising because numerous reports allege specific fibres as the postulated retino-hypothalamic pathway. The descriptions dealing with direct retino-hypothalamic connections are summarized in the table. They may roughly classified the following way : 1. In older reports, connections between the ventral or dorsal chiasmatic region and the central ventricular gray or the tuber cinereum were presented in several ways. The poor understanding of hypothalamic architecture, however, prevented reliable anatomical information about trajectory and termination of these fibres. A distinct separation between the chiasmatic fibres from the supra- and postoptic commissures and the complex intrahypothalamic fibre system was prevented by inappropriate methodological preparations. Descriptions of medullated fibres, which had been followed entering the tuber cinereum from the optic chiasma date back to over a century (WAGNER, 1 8 6 2 ; HENLE, 1868).

In 1 8 8 6 B O G R O W reported about an "Opticuswurzel" consisting of chiasmatic fibres and lost within the gray of the third ventricle. Using experimental methods, W L A S S A K ( 1 8 9 3 ) described unilaterally located degradation products within a fibre bundle of the optic tract taking the same destination as that of BOGROW. With regard to the overt misinterpretation of myologenesis and the nature of degeneration, the described granulated fibres may have been degenerated optic axons. 2. The retinal connection with the supraoptic ncl. has already been mentioned in section 1.3., describing accessory optic fibres. This bundle, observed in all vertebrate classes, is also known as "faisceau résiduaire anterieur" and "faisceau résiduaire de la bandelette" ( M A R I E and L É R I , 1 9 0 5 ) and as "fibres rétino-tangentielles" ( R O U S S Y and M O S I N G E R , 1 9 4 6 ) . The separation of fibres was reported to take place at the anterior rim of the optic chiasma.

3. M A R B U R G (1942) discovered a lateral retinotuberal tract. The fibres were traced disentangled from the total extension of the optic chiasma and were followed to the ncll. tuberis laterales (see footnote page 215). 4. Optic fibres separating at the posterior chiasmatic area were detected recruiting the medial retino-tuberal tract (MARBURG, 1942) or the "dorsale hypothalamische Wurzel" of F R E Y ( 1 9 3 7 — 1 9 5 1 ) . The field of termination corresponds to the medial tuberal nuclei or the periventricular, primary hypothalamic center of FREY. Degeneration of this bundle caused degeneration and loss of cells in the periventricular gray with subsequent dilatation of the optic recess and atrophy of the ependymal cell layers. Many authors ( J E F F E R S O N , 1 9 4 0 ; B L U M C K E , 1 9 5 8 ; H A Y H O W et al., 1 9 6 0 ) state that the trajectory of the bundle is a misinterpretation of the fibre architecture in the dorsal chiasmatic region, produced by tangential or horizontal section technique. According to the opinion of J E F F E R S O N the uncrossed, major portion of these fibres is composed of short internuclear, myelinated hypothalamic neurons of nonretinal origin. 5. KNOCHE ( 1 9 5 6 - 1 9 6 0 ) , BLUMCKE ( 1 9 5 8 , 1 9 6 1 ) a n d ( 1 9 5 9 ) described a retino-hypothalamic pathway as "vegetative Opticuswurzel" consisting of predominantly unmedullated axons. These fibres disconnect at the anterior margin of the optic chiasma and are characterized by their course through the terminal lamina. The authors thought that this pathway originates in specific, autonomic cells, corresponding to the photosensitive receptors with neurosecretory characteristics described by B E C H E R ( 1 9 5 3 , 1 9 5 4 ) . The axons were traced to various intrahypothalamic nuclear groups including the islets of MERGNER

GREYING (1926, 1 9 2 8 ) .

Similar fibres, ascending in the lamina terminalis were found by S O U S A - P I N T O and CASTRO-CORREIA (1970) in the rat. These fibres, however, could not be traced in the wall of the third ventricle passing to the infundibulo-tuberal region. 6. Especially numerous were findings collected in various fishes and amphibians stating a direct connection with the preoptic area (APO). The homology of this hypothalamic neuropil, receiving retinal afferents, seems not clarified in even same vertebrate classes (EBBESSON, 1967). It therefore seems not surprising that the so-called preoptic bundle has provoked similar controversy as other fibre bundles occupying the area between the antero-dorsal chiasma and the chiasmatic recess. H E R R I C K (1933 — 1939) homologized ithe preoptic fibres with the AAOT but later (1941c) conceded that the term AAOT for the

Accessory Optic and Retino-Hypothalamic System

225

probable connection of optic fibres with the epichiasmatic part of the preoptic ncl. in Amblystoma and Necturus has been unfortunate in view of the fact "that this connection is certainly different from the AAOT in mammals". He further wrote that "the confusion is increased by FREYS errors in identifying the axial optic tract

of amphibia with a supposed hypothalamic optic root". Nevertheless, that misleading name (AAOT)

was resumed by several authors (Riss et al., 1963; O'STEEN a n d VAUGHAN, 1 9 6 8 ;

PRINTZ a n d

HALL,

1.972) for a hypothalamic connection. F I T E a n d SCALIA (1976) s u g g e s t e d t h a t t h e a u t h o r s

describing this bundle in Anurans did misinterprete the course of the medial late crossing fibres. They pointed out that during the rearrangement of optic fibres within the CO a late crossing optic bundle appears separated from the main chiasmatic fibres in some section planes. These fibres do not cross until they reach the postero-dorsal margin of CO, where they are directed straight back and finally are to be followed rejoining the optic tract. This relationship of retinal fibres to the periventricular and suprachiasmatic part of the preoptic ncl. (pose) seems to correspond with the retino-hypothalamic connection t o t h e sc (CHU, 1 9 3 2 ; DE BOON, 1 9 3 8 ) , a l t h o u g h t h e

homology of both nuclei is questionable and in birds the topography of the sc has been obscure (see HUBER and

CROSBY,

1929;

CROSBY

a n d SHOWERS,

1969;

HARTWIG, 1 9 7 4 ) . BELLONICI (1888) d e s c r i b e d

optic

fibres splitting within the suprachiasmatic nucleus and has accurately depicted the relationship between traversing and surrounding optic and nonoptic fibres (fig. 2 a). He denied only the termination of optic fibres within this nucleus (as he did for the lateral geniculate body). Descriptions of optic fibres terminating within the sc followed t h e r e p o r t of TWITTY (1932) a b o u t

the

effects of heterografting eyes in Amblystoma. He

Fig. 2. Distribution of optic fibres within the suprachiasmatic area (ASC) 2-a. Reproduction of an etching obtained from BELLOXICI (1888), representing horizontal section through the ASC of the albino rat as revealed after osmium fixation and staining. (The original remarks were changed for sake of clearness.) BELLONICI'S comment was: " I n the mice and the albino rat, some fibres terminate within two rounded nuclei (the ncll. basales), formed by small neurons. These fibres form a very complicate pattern of ramification, necessitating very accurate evaluation and good histological material to differentiate them from the optic fibres" (p. 21). The outstanding representation of the wedge-shaped optic fibres ( " X " ) and the emerging accessory optic fibres (in original terms "optic fibres invading the tuber cinereum") earn to be emphysized. 2-b. Silver grain (SG) distribution overlying the ASC of the albino rat as revealed after mono-

cular injection of tritiated leucine. The section is obtained from approximately the same level as that of Fig. 2-a. The densely labelled biconcave area between both suprachiasmatic nuclei, containing the " X " - f i b r e s should be noted. The marked square comprises 1 mm 2 . Positive copy of dark field photomicrographs after intra vitreous injection of 25 [xCi 3H-leucine 10 days before sacrifice. Exposure time was 7 weeks. 2-c. Graphic representation of the SG densities within the square delimited in Fig. 2-b after photometric measurement. The graph comprises 10,000 measurements which were automatically obtained. I t was rotated clockwise by 30° corresponding to the angle of view of Fig. 2-b. The SG- density is increased steadily from the lateral half of the sc till it reaches its maximum within the optic tract. (Technique is described by MAI, 1976B.)

226

Mai, J . K.

found the gray matter near the entrance of the optic nerve usually altered in volume on the same side of the graft and stressed the intimate relationship between the optic chiasma and the gray matter dorsally to it. H E R R I C K ( 1 9 2 5 , 1 9 3 3 ) identified the corresponding fibre bundle (Fc. medialis nervi optici) between the optic chiasma and the preoptic region in Amblystoma. Later P A T E ( 1 9 3 7 ) described mild atrophy of the contralateral sc following eye removal in the cat, an observation which was later denied by F R E Y ( 1 9 5 0 ) in the guinea pig. F R E Y found atrophy in the ventricular gray matter next to the optic recess but no alteration on the sc proper. WENISCI-I and H A R T W I G ( 1 9 7 3 , 1 9 7 5 ) morphometrically analysed the sc of the rat and the mouse 6 days after bilaterale nucleation and found the diameter of sc-neurons decreased by 1 0 , 3 % . Contrary to this report are the findings of S T A N F I E L D and COWAN ( 1 9 7 6 ) in the rat. They stated that the position, size and general configuration of the sc were unchanged and the cells within them showed no evidence of transneuronal atrophy after survival times up to 240 days. This observation, made by S T A N F I E L D and COWAN after intraocular injection of tritiated amino acids raises the question whether the decrease in neuronal diameter estimated by W E N I S H and H A R T WIG (1973, 1975) reflects the response to either surgical stress on hypothalamic neurons or to "chemical" injury on sc-neurons by degraded material (GHETTI et al., 1973). Observations of distinct fibres to the SCA were confirmed by K N O C H E ( 1 9 5 6 — 1 9 6 0 ) in man, dog, and rabbit, using the B I E L S C H O W S K Y method, by R I E K E ( 1 9 5 8 ) in the rat, who reported terminal degeneration after applying the MARCHI and the B I E L S C H O W S K Y method and by D I V I R G I L I O et al. ( 1 9 5 8 , 1 9 6 4 ) in rat, guinea pig and cat, using silver impregnation technique after unilateral enucleation. These results have received further corroboration from histochemical studies by K I E R N A N ( 1 9 6 4 ) in the hedgehog. He traced a bundle of unmyelinated fibres, rich in acetylcholinesterase, which he suggested as being connected with the retina. It appeared to leave the dorsal aspect of the chiasma and to form a dense neuropil around the suprachiasmatic perikarya. He, however, did not exclude a non-optic origin from the post-optic decussations. Later, K I E R N A N ( 1 9 6 7 ) revised his earlier interpretation after surveying a wide range of vertebrates. Reviewing the literature he pointed out that previous reports failed the necessary variety of species and techniques, and he concluded that earlier studies might be misinterpretations of aberrant retinal or neurosecretory nerve fibres.

With his critical interpretation he anticipated various arguments against the value of degeneration methods for the elucidation of the question of direct retino-hypothalamic connections (NAUTA and HAYMAKER,

1969;

HENDRICKSON

et

al.,

1972;

SZENTA-

GOTHAI e t a l . , 1 9 7 2 ; M A I , 1 9 7 6 ) .

Like

J E F F E R S O N ( 1 9 4 0 ) , NAUTA and H A Y M A K E R stressed that the well known influence of ambient light upon certain hypothalamo-hypophysial functions need not be dependent upon direct retino-hypothalamic connections. After the introduction of the autoradiographic method for tracing fibre connections, the question of terminating direct optic fibres within the hypothalamus was reopened ( H E N D R I C K S O N et al., (1969)

1972).

The results obtained by autoradiography (ARG) give convincing support for the existence of a direct retino-hypothalamic connection. Whereas T U R B E S ( 1 9 6 5 ) in the rat and rabbit and G O L D B E R G and K O T A N I ( 1 9 6 7 ) in the frog failed to demonstrate labelling within the hypothalamic area, O ' S T E E N and VAUGHAN ( 1 9 6 8 ) described bilateral, extensive SG-distribution in the rat hypothalamus after intravitreous injection of tritiated serotonin. Following authors found the sc as the main recipient of direct retinal fibres (table). Since light microscopical A R G does not permit direct visualization of axons and their terminal ramifications, the course and distribution of retinal fibres traversing the sc at the ventrolateral margin and of the late crossing accessory optic axons have to be clearly differentiated from the presumptive hypothalamic in put. Surprisingly, the mere increase in the number of silver grains (SG) overlying the sc has been regarded as indicative for the termination of optic fibres. Additionally, the few quantitative studies on the SG-density of the SCA have been performed using a resolution unsuited to meet the conditions of that area, characterized by interwoven fibres and inhomogenously distributed pericarya (MAI, 1 9 7 6 ) .

To overcome the methodological restrictions inherent to techniques confined to light microscopy, SOUSA-PINTO

(1970),

HENDRICKSON

et

al.

(1972)

and MOORE and L E N N ( 1 9 7 2 ) have consecutively applied electron microscopical degeneration methods. Results achieved with this method are restricted by the possibility of generating artifacts and misinterpretations. Ultrastructural changes indicating degenerating axons or axon terminals within the "normal" visual system were seen consequent to operative (GRAY and H A M L Y N , 1 9 6 2 ) or mechanical lesions ( A K E R T et al., 1 9 7 1 ; H A R T W I G , 1 9 7 4 ) and chemical alterations of the afferent fibres (CUENOD et al., 1 9 7 2 ; GI-IETTI

Accessory Optic and Retino-Hypothalamic System

et al., 1972). Diverging results regarding the alleged termination of retinal fibres within either the arcuate ncl.

(SOUSA-PINTO, 1970)

or the

suprachiasmatic

ncl. as well as regarding the type of affected terminals within the same ncl. (MOORE and LENN, 1972; HARTWIG, 1974; GULDNER, 1977, personal communi-

cation) may be caused by these limitations. Electron microscopical ARG reveals the tissue in a more authentic condition, thus enabling statistical analysis of the sc-synapses (see section 2.3).

2.2. Morphology of the ncl. suprachiasmaticus observed light-microscopically

(sc) as

The sc borders the ventro-lateral aspect of the third ventricle dorsal to the optic chiasma. It has been described in the older literature as sc by RAMÓN Y CAJAL ( 1 9 0 3 ) , SPIEGEL a n d ZWEIG ( 1 9 1 7 ) , GRÜNTHAL

(1930),

KRIEG

(1932)

and

D E BOON

(1938).

It corresponds to the ncl. basalis of BELLONICI (1888) the ncl. anterieur principal of RAMÓN Y CAJAL (1911), t o t h e ncl. T y of FRIEDEMANN (1.912), t o t h e ncl. in-

fundibularis medialis of WINKLER (1914), to the noyau

accessoire supraoptique (1925),

t o t h e ncl.

RIOCH

(1929),

of Foix and NICOLESCO

ovoideus of GURDJIAN

INGRAM et

al.

(1932),

to

(1927), the

ncl.

preopticus periventricularis pars suprachiasmatica of CHU (1932), to the ncll. infundibulares posterior et caudalis of ROSE (1935), to the ncl. suprachiasmaticus ventralis of KOIKEGAMI (1937) and to the

ncl. prothalamicus periventricularis

ventralis in-

ferior of BROCKHAUS (1942).

A comparative study of this ncl. in different verte-

brate classes is to be found in CROSBY and SHOWERS

(1969). Their description discloses that in lower vertebrates the suprachiasmatic nuclei or their homologies are interconnected by strands of subventricular commissural cells. The development of the sc reaches its peak in reptiles, carnivores and rodents. The prominent appearance of the sc in carnivores and rodents was already expressed in the comparative studies of BELLIONICI (1888) and SPIEGEL and ZWEIG (1917). In some animals, like the

urodeles, the sc was not yet distinguished. In birds, the sc needs still to be characterized (MEIER, 1973;

OKSCHE et al., 1974). In mammals, the sc stands out

by the dense accumulation of darkly stained small to medial sized cells at the medial border. The ventral part of the ncl. is more or less embedded into the dorsal chiasmatic plate, the depth of embedding seems to correlate with the extent of development of the ncl. Myelinated chiasmatic fibres may therefore be observed, mostly accompanying the much

227

more numerous unmedullated fibre bundles. In the verymost anterior portion of the sc no subventricular interconnecting gray is discernable and the cells appear immediately subjacent to the ependymal cell layer of the third ventricle. Reviewing the literature, there may be found some hints that the sc is not as well delimited as generally described and is not exclusively composed of isomorphous cells. In the most anterior portion of the sc the cells quite often merge with the neighboring medial preoptic ncl. (RIOCH, 1925) thus engendering some confusion about the morphological delineation of the anterior portion. Separate names were therefore introduced, like ncl. praeopticus suprachiasmaticus, (see page 225), ncl. suprachiasmaticus diffusus (HUMPHREY, 1936),

or preoptico-anterior-hypothalamic continum (HEIMER a n d LARSSON, 1966).

In some animals the marginal lnteral area of the suprachiasmatic ncl. appears invaved by cells of larg e r size. (see CROSBY a n d SHOWERS, 1 9 6 9 ; MAI a n d JUNGER, 1 9 7 7 ) . OKSCHE et al. (1974), in a d i a g r a m -

matic representation of the rostral hypothalamus in passerine birds, depicted magnocellular neurons in the transition zone of the supraoptic ncl. and the ventrolateral part of the sc and described the medial preoptic ncl. as continuous with the anterior hypothalamic area. In the albino rat, the nuclear population of the ncl. can be divided into darkly stained parvocellular material comprising most of the ncl. and giving this ncl. its prominent appearance, and into more polygonal cells, surrounded by a rather lightly stained cytoplasmic rim, found more loosely arranged in the ventro-lateral part of the ncl. and merging with the cells of the ventral division of the anterior hypothalamic ncl. (ha) and the lateral hypothalamic ncl. (hi). Experimental evidence also favours the concept of intimate relationship with extrasuprachiasmatic neuropil. BARRY et al. (1974) showed that the distribution of LH —RH containing neurons in the guinea pig centered in the suprachiasmatic neuropil but formed part of the prechiasmatic and preoptic group. SWANSON (1976)

observed that

stereotactically

applied precursors, confined to the ventral periventricular neurons of the rat, labelled a group of fibres which were virtually identical in distribution to the projection of the anteriorly adjacent sc. He concluded that the sc may be essentially a component of the periventricular ncl., differentiated by an input from the retina.

228

Mai, J. K.

On the other hand, it is apparent from autoradiographic studies that characteristic inhomogeneities of preterminal elements of extrinsic fibre systems within the sc proper exist (see below). Such disagreement between morphologically "isomorphous" nuclei and the disclosure of subdivisions after experimental approach became evident in many subcortical visual areas after the introduction of the autoradiographic tracing method and was already mentioned by S T U M P F ( 1 9 6 8 ) with regard to the ventro-medial hypothalamic ncl. Further evidence for a heterogeneous neural population within the confine of the sc was given with regard to the localization of neurophysin containing somata ( V A N D E S A N D E et al., 1 9 7 4 , 1975;

B U R L E T a n d MARCHETTI, 1 9 7 5 ; W E I N D L

etal.,

and

of neurotransmitters (Loizou, 1 9 7 2 ; SAAVEDRA et al., 1 9 7 4 ) , of developmental (HYYPPA, 1969) and of reactive changes ( H A R T W I G , 1 9 7 5 ; RAISMAN, 1 9 7 5 ) . S O F R O N I E W , 1 9 7 6 ; ZIMMERMAN

1976),

2.3. Electron microscopic studies of the tic nucleus

suprachiasma-

The ultrastructure of the mammalian sc has been described by several investigators in normal and experimental conditions in the rat (SUBURO and I R A L D I , 1 9 6 9 ; L E B E U X , 1 9 7 1 ; HENDRICKSON etal., 1 9 7 2 , MOORE a n d K L E I N , 1 9 7 2 ; G Ü L D N E R a n d W O L F F , 1974;

CLATTENBERG

et

al.,

1976;

GÜLDNER,

1976;

MAI, 1 9 7 6 ; MAI a n d J U N G E R , 1 9 7 7 ; LENN e t al., 1 9 7 7 )

and rabbit (CLATTENBURG et al., 1 9 7 2 , 1 9 7 5 ) . The diameter of somata of randomly selected neurons were determined in the rat ranging from 5 — 1 2 |J.m ( S U B U R O

rabbit

and

IRALDI,

1969)

and

in

the

from

6.5 (xm—14.2 |xm averaging 10.6 ± 0 . 1 2 [IM (CLATTENBURG et al., 1972). The nuclei in the rat had a mean diameter of

7 . 4 3 ¡ x m ± 0 . 0 9 (zm

(CLATTENBURG

et

al.,

1972).

It

was observed that the nuclei were arranged polarily with their long axis oriented from medio-ventral to dorso-lateral ( M A I , 1 9 7 6 ) . They commonly show one or more deep identations. The large nucleolus is often in contact with the nuclear membrane. "Pale" and "dark" neurons were described in both the male ( S U B U R O and I R A L D I , 1 9 6 9 ) and the female rat sc (CLATTENBURG et al., 1 9 7 6 ) . The greater electron density of "dark" neurons was ascribed to the presence of a larger amount of ribosomes and neurotubules in their cytoplasm, showing evidence of enhanced synthetic activity. The types of terminals to be observed within the sc together with their topological arrangement have been extensively studied by G Ü L D N E R ( 1 9 7 6 ) in the adult and by L E N N et al. ( 1 9 7 7 ) in the newborn rat. According to the

results of degeneration studies by

HENDRICKSON

et al.

( 1 9 7 2 ) , MOORE a n d L E N N ( 1 9 7 2 ) a n d H A R T W I G ( 1 9 7 4 )

and to correlative studies on other subcortical visual centers G U L D N E R suggested that the retino-hypothalamic fibres terminate in asymmetrical synapses containing clear vesicles and mainly type-L mitochondria. Supporting this view were the observations by M A I ( 1 9 7 6 ) that SG after intraocular injection of tritiated leucine were mainly observed overling asymmetrical synapses containing clear vesicles and pale mitochondria and by L E N N et al. ( 1 9 7 7 ) that asymmetrical synapses appeared at the time of the arrival of retino-hypothalamic fibres. Quantitative study of labelled synapses within the sc seem to establish that suspicion (MAI and GULDNER, in progress). If the correlation between retino-hypothalamic and presumptive "optic" synapses (Gray-type I with presynaptic elements containing type L mitochondria and clear vesicles) turns out to be correct, then probably 1/6 of the terminals within the sc originate from retino-hypothalamic fibres. Whereas the terminals appear evenly distributed when no differentiation is made ( M A I and J U N G E R , 1977) light microscopical analysis of labelled retinal terminals revealed accumulation of radioactivity within the ventro-lateral and the caudal sc (see MAI, 1 9 7 6 ) . Serotoninergic synapses seem also concentrated within the ventral sc ( F U X E , 1 9 6 5 ) , there probably exerting inhibitory influences on sc neurons, already excited by visual stimuli as suggested by N I S I I I N O a n d KOIZUMI ( 1 9 7 7 ) .

It has not yet shown whether the high concentration of serotonin found in the sc-terminals is associated with DCV within the sc of the rat (FUXE, 1965; DAHLSTROM 1969; BURG

FUXE

etal.,

and and

FUXE,

1964;

HOKFELT,

AGIIAJANIAN

1969,

1970;

et

al.,

CLATTEN-

1972).

et al. (1.974) by microdissection and microassay of the rat sc estimated a serotonin content within the central 200 ¡xm of the ncl. that doubled the remaining 400 ¡xm external layer. SAAVEDRA

2.4. Efferent fibre connections of the nuclei

suprachiasmatic

Silver impregnation methods of the rat sc (KRIEG, 1 9 3 2 ; SZENTAGOTHAI et al., 1 9 7 2 ) have not visualized axons for any significant distance outside the sc. Axons were observed as directed postero — dorsally in sagittal plane, with no initial collaterals discernable, and became lost within the precommissural component of the stria terminalis. K R I E G believed that they might contribute to the posterior part of the periventricular tract. K R I E G ' S view is supported

Accessory Optic and Retino-Hypothalamic System

by degeneration studies applied by SZENTAGOTHAI et al. (1.972) in the cat. After lesions placed in the medial hypothalamic nuclei they found considerable amount of degenerated axons in the anterior component of the periventricular fibre system. These fibres were observed ascending in antero-dorsal direction and joining the stria medullaris thalami. With regard to recent studies of H E R K E N H A M and NAUTA ( 1 9 7 7 ) , however, the proposed continuation of degenerated fibres in the stria medullaris may be due to artefactual transsection of fibres originating within the lateral hypothalamic ncl. SWANSON and COWAN ( 1 9 7 5 ) claimed to have succeeded in placing a small quantity (0.4 (iCi) of tritiated prolin exclusively within the sc, largely confined to its ventro-lateral sector. No label was found anterior to the suprachiasmatic ncl., an observation, which is quite contrasting the results obtained by CONRAD and P F A F F ( 1 9 7 5 ) in the albino rat and by B E R K and B U T L E R ( 1 9 7 7 ) in the pigeon. All SG outside the limits of the rat sc were found ipsilaterally either over the periventricular area immediately medial, dorsal and caudal to the ncl., or in a narrow band along the ventral aspect of the hypothalamus ventral and lateral to the ventromedial ncl. reaching the margins of the dorso medial and arcuate nuclei and labelling in small amount the internal lamina of the median eminence and the rostral part of the median forebrain bundle. Interestingly, they reported a complete overlap of the label distribution with the outflow from the medial preoptic and the anterior hypothalamic areas. Whereas CONRAD and P F A F F stressed marked differences in the fibre distribution of both areas. This may, however, also reflect peculiarities and factors limiting the application of the autoradiographic method for studies within the hypothalamus. Since diffusion of labelled precursors may induce uptake in distant neurones or may mask fibre paths. During our own studies on the efferent fibres of the sc after stereotaxic application of tritiated leucine in small amounts and survival rates ranging from 2 hours to three days (unpublished) there could be observed that even in those cases, where the injection area appeared rather confined, unspecific label-spread occured, and that SG localized also over neuronal pericarya distant from the site of injection. Finally, the tissue damage, even with the use of beveled micropipettes, and local irritation as reflected by glial reaction may constitute factors promoting diffusion or vascular spread and preventing the delineation of "characteristic" axons. Until these restrictions, inherent in hypothalamic neuronal labelling, may be eliminated by other methods, the results of SWANSON and COWAN, indi-

229

cating, that the efferent sc-fibres swarm out in a diffuse manner so that the whole periventricular hypothalamic area becomes filled with SG, must remain authoritative. Their results, however, corroborate the possibility of a direct fibre connection to the hypothalamic hypophysiotropic area (HTA, HALASZ, 1969) via the infundibular tract (the suprachiasmatic fascicle of Loo, 1931). This possibility is based on endocrinological disturbances following lesion of the sc (CRITCHLOW a n d D E G R O O T , 1 9 6 0 ; CRITCHLOW,

1963;

WURTMANN, 1967; see below) and on microscopic immunocytochemical studies (BARRY et al., 1975). Controversial results were reported after application of H R P into the region of the ventro-medial hypothalamic ncl. (hvm). SWANSON and COWAN (1975) failed to adequately label neurons in the sc of the rat, but they gave some explanations that this failure does not disclose fibre distribution to the hvm. G U P T A (1976), who placed H R P within the hvm of the cat observed labelled neuronal cell bodies exept other regions within the ipsilateral sc, anterior hypothalamic ncl. and the anterior preoptic area. These differences obviously reflect methodological improvements and not species differences between these two mammals as in the organization of other subcortical "optic" connections ( R I B A K and P E T E R S , 1975).

2.5.

Non-retinal

afferents

to the

suprachiasmatic

nucleus

The afferent fibres, as studied by neuroanatomical methods are more precisely defined. Studies of normal silver impregnated material ( G U R D J I A N , 1 9 2 7 ; K R I E G , 1932) in the rat revealed that the sc seems intimately related to the supraoptic complex of fibres and that it receives fibres from the supracommissural and preoptic components of the latter. B y precommissural fibres of the stria terminalis and by corticohypothalamic axons the sc is probably supplied with noradrenergic fibres (JACOBOVITZ, 1 9 7 5 ) . Other sources of sc-afferents were identified using degeneration studies. After placing lesions in the habenular region and in the anterior midbrain gray matter of cats degenerated fragments were followed by S Z E N TAGOTHAI et al. ( 1 9 7 2 ) along the route of the posterior component of the periventricular system (KRIEG, 1932) to the sc. Although the origin of these afferent fibres remained obscure, the authors held the opinion that they were of mesencephalic origin, some of them projecting by a dorsal route which passes through the habenular nuclei.

230

Mai, J . K.

The mesencephalic origin of the serotonin containing terminals within the sc was established by fluorescence histochemistry ( F U X E , 1 9 6 5 ; A N D E N

2.7. Functions of the suprachiasmatic

e t a l . , 1 . 9 6 6 ; BAUMGARTEN a n d LACHENMAYER,

The functional significance of a direct retino-hypothalamic connection has been mentioned by numerous authors (see table and part 2.1.). Already in 1942, the intimate relation between the optic system and the suprachiasmatic area (ASC) was pointed out by HERRICK: " I n the chiasma ridge there is an intricate neuropil which receives terminals and collaterals from the optic tracts and all components of the postoptic commissure and from the surrounding regions. This is evidently a strategic point of integration of all hypothalamic function." Today, it is firmly established that the hypothalamus is the focal point at which neural stimuli and endocrinal feedback mechanisms converge to influence the pituitary. In mammals, at least nine hormonal substances exert positive or negative releasing effects on the anterior pituitary hormones. While the role of the hypophysiotropic area (HTA) remains unchallenged as the preeminent mechanism whereby the hypothalamic hormones gain access to their respective cells in the anterior pituitary, the contribution of the sc neuropil in hypothalamic regulation of the adenohypophysis remains hitherto only suggestive. The elaboration of the sc as target of retinal fibres together with indirect evidence of photo-neuroendocrine events propagated by this pathway have focused attention towards the participation of the sc on neuro-endocrine regulation. Data on the suprachiasmatic influences have been mainly obtained using indirect methods. Those which were repeatedly applied were:

DAHLSTROM

electron

and FUXE,

microscopic

1974;

HOKFELT,

degeneration

et al., 1969) a n d b y A R G

1972;

1974),

by

(AGHAJANIAN

(AZIMITIA, 1 9 7 5 ) . T h e

pre-

sence of large dense core vesicles in most degenerating endings after dorsal and median raphe lesions indicates the involvement of endings which take up or contain serotonin (AGHAJANIAN and BLOOM, 1 9 6 7 ) . It remains, however, unclear to what degree the raphe nuclei contribute to the overall content of sc serotonin since other structures which are related to the sc, as the ependyma, synthesize serotonin, which in turn may be taken up by noradrenergic nerve terminals ( K N I G G E et al., 1 9 7 5 ) . An other tract, projecting to the sc has been found to originate in the ventral lateral geniculate nuclei (cglv) and Z I of rat and cat ( G R A Y B I E L , 1 9 7 4 ; SWANSON a n d COWAN,

1974;

RIBAK and PETERS,

1975).

These fibres project via the commissure of M E Y N E R T to both sc. The localisation and the type of the presynaptic elements are still unknown. By NAUTA technique ( K N O O K , 1 9 6 5 ) and by A R G bilateral projection to the sc was revealed from the medial septal area in different animals (GARRIS and M I T C H E L L , 1 9 7 6 ; K R A Y N I A K , 1 9 7 7 ) and from the hippocampal cortex (AZMITIA, 1 9 7 3 ) . Verifying electrophysiological findings of a projection of the HTA, including the hvm, to the ASC ( D Y E R , 1 9 7 3 ; MAKARA and HODACS, 1 9 7 5 ) . From an area rostral to the hvm (A 14 DAcells) dopaminergic fibers innervating the anterior part of the sc in the rat were observed to originate (BJORKLUND et al., 1975).

In most cases, where the topographical arrangement of the afferent fibres was studied, a highly localized distribution of presynaptic elements within the sc was observed. Studies after intraocular precursor injection have revealed projection areas confined to the ventral (ventrolateral) and posterior division of the sc (see table). Midbrain afferents were found in the posterior aspect, whereas noradrenergic boutons were accumulated in the lateral areas of the sc (BAUMGARTEN, 1976).

2.6. Retinal afferents to other hypothalamic

nuclei

Since only the sc is firmly established as target of retinal afferents in a wide range of vertebrates, no further remarks will be given here about further connections and possible functions of the other nuclei, listed in the table.

A. Methods used to study the functions

nucleus

of the sc

1. The evaluation of the influences of external or internal stimuli or of deprivation on the ultrastructure of the sc. Here, the effects of various environmental lighting regimens as well as the effects of experimental hormonal conditions may be summarized. 2. Analysis of the enzyme activity during various endocrinological and behavioral states e. g. the estrous cycle (PACKMAN et al., 1976). 3. Experiments based on deafferentiation of the sc. To this group belong endocrinological studies concerned with the effects of blindness in animals and man as well as degeneration- and autoradiographic studies after unilateral enucleation. Most knowledge about the morphological and functional reorganization of the sc afferents was obtained thereby (MOORE, 1974; S T A N F I E L D and COWAN, 1 9 7 5 ; MAI, 1 9 7 7 ; SILVER,

1977).

4. The functional significance of the contributory

Accessory Optic and R e t i n o - H y p o t h a l a m i c S y s t e m

part played by the sc in hypothalamic function has been confirmed primarily through studies in which careful electrolytic or surgical lesions were placed into the sc, thus destroying all or parts of the sc, or the efferent axons were disrupted. Since different indices were employed by the various investigators fo rthe descriptions of the areas lesioned, only a restricted amount of information can be applied to the sc. Bilateral lesions of the sc of normal animals have been effective in release of gonadotropins and of ACTH (see below), in depletion of the sexual activity in male rats (LISK, 1967) and in inducing constant vaginal estrus (see ANTUNES-RoDRiGUEsandMcCANN, 1 9 6 7 ) . The lesions resulted in changes of circadian rhythms, e.g. desynchronization of the pineal Nacetyl-transferase (NAT) activity (MOORE and K L E I N , 1 9 7 4 ) , of the adrenal corticosterone rhythm (see below), of the sleep-wakefulness cycle (STEPHAN and ZUCKER,

1972;

IBUKA

and

KAWAMURA,

1975)

and

of the drinking and locomotor activity (STEPHAN and Z U C K E R , 1 9 7 2 , S I L V E R , 1 9 7 7 ) . Numerous studies were designated in evaluating the effects of sc-lesioning in animals whose hormonal regulation had been disturbed experimentally ( A N T U N E S - R O D R I G U E S and MCCANN, 1 9 6 7 ; CRITCHLOW, 1 9 6 9 ) .

The methods, summarized within the last two groups, although highly informative on the complex integrated neural mechanisms modulating pituitary function, have to be considered as rather ambiguous. Contrary to the experiments, where only the optic nerve and its well known projection area is affected, those damaging the sc affected almost without exeption with the intrinsic and extrinsic neuronal network the AOS-fibres, the infundibular tract, the ependymal wall including the highly spezialized ependym of the supraoptic recess, the neurons propagating the impulses toward the target neurons, possibly neurons transporting neurosecretory material, and interfered with the blood supply of the region. Direct injury of the HTA and nonspecific effects, e.g. by stress (DONOVAN, 1970) or persistent irritation ( E V E R E T T and R A D F O R D , 1 9 6 1 ) , may also occur. The interpretation of results is further complicated because the effects observed may be due to either stimulation or destruction of nerve cells located in the affected area. Finally, the effects of sc lesioning were observed after destruction or deafferentiation not only of sc, but also of extrasuprachiasmatic loci. 5. Lot of information stems from electrophysiological observations. Whereas former investigators merely succeeded in revealing evoked potentials within

231

defined hypothalamic nuclei (GERARD et al., 1936; MASSOPUST a n d D A I G L E , 1 9 6 1 ; F E L D M A N , 1 9 6 4 ) ,

the

anatomical demonstration of the direct retinosuprachiasmatic projection has enabled electrophysiological analysis directed to specific objectives (NISHINO e t a l . , 1 9 7 5 , 1 9 7 6 ; B R E M E R , 1 9 7 6 ; NISHINO and

KOIZUMI,

1977;

SAWAKI,

1977;

YAGI

and

SA-

WAKI, 1 9 7 7 ) .

6. Effects of hormones implanted (LISK, 1967; et al., 1974) or of substances iontophoretically applied to the sc (section 2.7.E). Since various experimental designs listed before demonstrated involvement of the ASC in hormonal guided behavior, it became particularly important to ascertain, if specific hormone-sensitive elements are located within the ASC and what hormones brought about specific responses. FERIN

7. Microscopic immunocyto- and immunohistochemistry and ARG offered the possibility to study the anatomical distribution of hormonal target cells (see below). B.

Suprachiasmatic

influences

on gonadotropin

secretion

The ASC has been postulated as an important component of the diffuse neuronal system, occupying the septum pellucidum, medial preoptic and anterior hypothalamic area regulating the cyclic release of gonadotropins. This system is conceived to originate diffusely throughout the septal complex, to converge somewhat as it traverses the anterior preoptic and anterior hypothalamic region (AHA) and to enter the HTA (hypophyseotropic area, HALÀSZ) via the long axons of the LH —RH synthesizing pericarya by way of the infundibular tract (TI) (SZENTÀGOTHAI e t a l . , 1 9 6 8 ; et

al.,

1975;

L E O N A R D E L L I e t a l . , 1 9 7 3 ; MCCANN

EVERETT,

1976;

KALRA,

1976).

The

participation of the sc in modifying the activity of the cells of the HTA is suggested by investigations showing that electrical stimulation in the ASC induces ovulation (EVERETT et al., 1965), and in contrast, that electrolytic or mechanical lesions placed on the ASC produced in normal cycling females a state characterized by depletion, at least reduction, of L H — R H in the HTA, followed in the female by the inability to mobilize enough LH for evulation and formation of corpora lutea ( R A L P H and F R A P S , 1959a, b; M E S S et al., 1966; MARTINI et al., 1968; MCCANN e t a l . , 1 9 6 8 ; B U T L E R a n d DONOVAN,

1969;

et al., 1969). In the male, elimination of mating behavior with gonadal atrophy has been reported after destruction of the APO and ASC (SOULAIRAC, 1956). Corresponding results were obtained by placing lesions in the sc of animals whose SCHNEIDER

232

Mai, J. K.

hormonal regulation had been disturbed experimentally (BARRACLOUGH and G O R S K I , 1961.; S C H N E I DER et al., 1969). The question remained whether these effects were elicited merely by stimulation or transsection of fibres passing through the ASC, and/or involvement of structures with quite different functional properties (as the sympathetic area B, neighbored by the parasympathetic areas A and C) which lie next together and probably merge within the ASC (BAN, 1966). There exists some other evidence, however, that mechanisms which influence the gonadotropin secretion, at least partly reside within the sc. C L A T T E N B U R G and coworkers (1971 — 1976) found ultrastructural changes indicating inhanced intraneuronal synthesis in rabbit and rat sc-neurones under various conditions in which the serum-LH levels were elevated. These signs were interpreted as indicative for the synthesis of LH—RH. Interestingly, the changes were observed mainly in neurons surrounding blood vessels. That localization coincides with the distribution of Gn—RH in the immunohistochemically analysed organum vasculosum of the mouse brain (GROSS, 1976). In a passerine bird, O K S C H E et al. ( 1 9 7 4 ) found a huge amount of secretory nerve cells in various parvocellular nuclei of the AHA, including the sc. The authors, however, were not able to demonstrate whether these secretory neurons contribute to the anterior hypothalamic tract that can be traced to the avian median eminence ( W I N G S T R A N D , 1 9 5 1 ; OKSCHE a n d FARNER, 1 9 7 4 ) .

The neurosecretory activity of the sc is indirectly demonstrated by the fact that the developmental changes of this ncl. in perinatal, neonatal and infant female rats are congruous with those of the ventromedial and arcuate ncl. whose relationship in the control of gonadotropin secretion is well established (MORISHITA e t a l . , 1 9 7 6 ) .

Tuberoinfundibular neurons in the sc have been identified by antidromic stimulation of the median eminence ( Y A G I and SAWAKI, 1 9 7 0 ; MAKARA et al., 1 9 7 2 ; D Y E R , 1 9 7 3 ) . The latter author antidromically activated not only APO—AHA neurons of the rat, but also those located in the sc. The neurons were characterized by their very slow discharge rate, when contrasted with adjacent cells. The strongest support to the suggested role of the sc in Gn-release was given by direct visualization of LH —RH containing neurons originating within the guinea pig and rat sc and projecting to the HPTA ( B A R R Y et al., 1974; K A L R A , 1976). It may be objected that the anatomical distribution of pericarya, immunoreactive with antisera to synthetic LH —RH, within the sc may be due to

false positive reactions since the specifity of the various methods applied to localize GnRH by immunohistochemistry or immunofluorescence is not pronounced ( G R O S S , 1 9 7 6 ) , and since in most publications reviewed, the sc is not mentioned as belonging to areas where GnRH was observed. The GnRH reactive cells may be, on the other hand, rarely identified by all antisera applied. HOFFMANN ( 1 9 7 7 ) presented evidence that in different animals and with different antigenic determinants of antisera used for identification of GnRH-neurons, populations were marked, which differed in regard to localization and physiological properties. Whereas in some animals as the rat and mouse two fields were revealed, which in bioassay also displayed differential LH and FS release, in other animals, L H — R H and F S —RH seemed present in the same cells, which were, however, concentrated differently in various animals. Other studies are indicative for an anatomical dissociation of neurons controlling gonadotropin activity in males and' females (CHAPPEL and B A R R A CLOUGH, 1 9 7 6 ; G O R S K I e t a l . , 1 9 7 7 ; NANCE, 1 9 7 7 ) .

The results obtained in the studies about the anatomical distribution of estradiol 1 -concentrating cells have not served to corroborate in favour of suprachiasmatic influences on the feed back mechanism of the gonadotropin secretion. Biochemical techniques have clearly shown that synthesis and release of hypophysiotropic hormones are governed by the amount of estradiol reaching the receptors. These neurons displaying nuclear binding of estradiol probably form the cellular substrate for the formative action of sex steroids during embryonic life on certain brain functions as the control of sexual and emotional behavior and Gn secretion (PETRUSZ, 1975; L I T T E R I A , 1 9 7 7 ) . It is not yet known whether the estradiol binding sites are the critical targets for neurons triggering ovulation as suggested by anatomical and physiological properties (see K E L L Y et al., 1 9 7 5 ) . This nuclear binding can be visualized in the ARG prepared from sections of the target tissue. The "hormone-architecture" of the brain of various animals was studied under normal and experimental conditions. It was found that estradiol concentrating cells are located within the APO—AHA continuum and send fibres to the periventricular system ( G R A N T and S T U M P F , 1 9 7 5 ) as the neurons of the sc do (section 2.4.). The cells located within the well defined sc obviously do not concentrate 1 Androgens seem distributed in the same hypothalamic areas as those containing estrogen by autoradiographic analysis ( G R A N T and S T U M P F , 1 9 7 5 ) . 3H-progesteron uptake was demonstrated by ARG in neurons of the ncl. preopticus suprachiasmaticus in guinea pig brain (SAR and S T U M P F , 1973).

Accessory Optic and R e t i n o - H y p o t h a l a m i c S y s t e m

estradiol, although dispersed labelled cells were found near its junctions with the periventricular and

preoptic

ncl.

(KEEFER

and

STUMPF,

1975;

and SAR, 1975a; STUMPF et al., 1975). On the other hand, the fact that the sc obviously receives afferents by the ventral ascending noradrenergic bundle speaks indirectly for such a relationship. Since all other hypothalamic areas which are supplied by this fibre system generally contain estrogen target neurons — which seem to be influencSTUMPF

ed b y t h i s s y s t e m (GRANT a n d STUMPF, 1975) —,

this may well be valid for the sc. The failure to demonstrate target neurons in the sc possibly relies on the innervation of dendritic branches of sc neurons, which extend outside the limits of this nucleus (HENDRICKSON et al., 1972). In the case that the estrogen target cells constitute the neurons responsible for sexual and emotional behavior, it has to be questioned, whether the retinal afferents which innervate the sc impinge directly on the hormonally addressed cells. If the neurons postsynaptic to the retinal afferents, do not directly influence Gn secretion and do not directly come under endocrine feed back control, either the "intrinsic" sc system ( G U L D N E R and W O L F F , 1 9 7 4 ) or the direct retino-anterior-hypothalamic connection (CONRAD a n d

STUMPF,

JUNGER, 1977)

1975;

MAI,

1976,

MAI

and

may account for the photo-gonado-

233

costerone was found to correlate with the appearance of degenerated synapses within the sc after orbital enucleation (CAMPBELL and RAMALAY, 1 9 7 4 ) . A D E R ( 1 9 7 5 ) reported that the circadian lightsynchronized rhythm which under normal conditions was observed between the 22 and 25 days of age in the rat was accelerated by environmental stimulation. Since it is well known that the outgrowth of nerve fibres and the formation of synapses are enhanced under various stimuli (see LEVI-MONTALCINI, 1 9 7 6 ) this acceleration is very compatible with the suggestion of an earlier formation of a functioning connection between the retina and the sc by the regimen applied. Recent studies using more reliable methods have, however, shown that the optic innervation of the sc occurs around postnatal day 4 in the rat (FELONG, 1976;

STANFIELD a n d

COWAN,

1976;

LENN

et

al.,

and the hamster (So et al., 1 9 7 7 ) . L E N N et al. ( 1 9 7 7 ) have therefore doubted the correlation between the formation of functioning synapses and the onset of rhythmic changes in plasma corticosterone levels. It seems that the generation and maintenance of the adrenal corticosterone rhythm relies on mechanisms which also involve the midbrain reticular formation (page 232), the pineal (see PIECHOWIAK, 1 9 7 3 ) and the adrenal itself 1977)

(SIOTSUKA e t a l . , 1 9 7 4 ) .

tropic response. C. The sc and the development and maintenance serum corticosterone rhythm

of the

adrenal

While the precise anatomic sites controlling A C T H secretion — assuming that such loci are not diffuse — remain to be determined (see DONOVAN, 1970; GRIZZLE et al., 1974), it is clear that the sc is not directly involved in the mechanisms governing the total output of A C T H . As is the case for estradiol, neurons in selected brain regions exhibit nuclear uptake of 3H-cortisol but obviously no accumulation within the ASC has been observed (STUMPF and SAR, 1975b). Since, however, MOORE and E I C H L E R ( 1 9 7 2 ) described the suppression of the daily adrenal rhythm in the adult rat consecutive to bilateral sc lesions, several investigations have supported their view of the responsibility of the direct optic projection to the sc for the circadian rhythmic changes of corticosterone secretion. H I L F E N H A U S ( 1 9 7 6 ) showed that the light-dark cycle is the dominant synchronizer of the plasma corticosterone level, as evidenced by the complete inversion of the rhythm obtained under inverted light-dark cycle. In earlier studies the onset of the circadian changes in plasma corti-

D. Mediation of other light-induced hormonal and behavioral circadian rhythms and the question of interacting retinohypothalamic and accessory optic fibres.

Desynchronization of several other rhythmic events has been observed after destruction of the sc (see 2.6.4.).

In this context, it has once more to be repeated that there were no lesions-effective in rhythmic desynchronization — performed which did not additionally destroy the late crossing accessory optic bundle ("X"). While the interpretation of the consequences of sc lesioning did not consider the bulk of destroyed AOS-fibres which regularly would supply the ventral tegmental area, this failure is not eliminated by the interpretation of results after lesions placed in the region of the trajectory of the accessory fibres. In the latter case, the superficially arranged fibres had been transsected, the ATV, however, was not totally deprived from influences mediated via the late crossing and deep coursing accessory fibres. Since these experiments were performed on rodents, where the inferior fascicle of the AOS is markedly developed, the perceived function of the sc could therefore well be generated by masked AOS-fibres.

234

Mai, J . K .

Therefore, all these sc-lesions interfered with midbrain regulations, and it is difficult to assess the effects of sc lesioning on the role played by the sc in the entrainment or initiation of rhythms. The importance of the late crossing AOS fibres was demonstrated by L I S K ( 1 9 6 7 ) who found that hormone implantations to both sc regularly initiated lordosis behavior in rat except in two animals. " I n these two", L I S K writes, "hormone placement was similar to the others, but there appeared to be a small lesion of the median peak of fibres between the suprachiasmatic nuclei produced by one of the hormone bearing tubes". The eminent role of the midbrain tegmentum, supplied by the AOS-fibres, is accentuated by the distribution of radioactivity after systemic in vivo administration of tritiated progesterone in mouse, rat and guinea pig. The radioactivity determined in the midbrain exceeded t h a t in the hypothalamus ( s e e SAR a n d STUMPF, 1 9 7 5 b ) .

The importance of the midbrain in the regulation of ACTH secretion was summarized by MANGILI and coworkers (1966). They stressed the tonic inhibitory action of the midbrain which thereby might participate in controlling the circadian rhythmic changes of adrenal secretion. Since the rhythmic pattern of day and night active animals closely resembles t h a t of night active animals, if related to the state of sleep and activity (even though a 12h-shift exists typical for the nocturnally active species) the rhythmicity of midbrain acitivity during sleep and wakefulness may itself be influenced by the reticular activating components in the midbrain. Studies of H I L F E N H A U S ( 1 9 7 6 ) have indicated that rats kept under sodium restriction with a more than 100 fold increase of the plasma angiotensin concentration exhibited significant aldosterone rhythm well synchronized with the corticosterone rhythm but not with any rhythmic changes in the reninangiotensin system. While the renin-angiotensin system is the dominant regulator of aldosterone secretion in the rat (CAMPBELL et al., 1 9 7 4 , 1 9 7 5 ) , this rhythmicity was explained by the concept of a forebrain-hypothalamus-midbrain circuit mediating thirst initiated bj' activation of the renin-angiotensin system (KUCHARCZYK and MOGENSON, 1 9 7 7 ) . They brought electrophysiological and anatomical evidence supporting the idea of a feedback mechanism in which signals of the forebrain receptors for angiotensin are directly mediated to the ventral tegmental area. There, these command signals" may be integrated with cyclic accessory optic, with forebrain, and coordinating motor patterns before influencing the phasic hypothalamic ACTH secretion. The additional role of the midbrain rhythmicity

could help to explain why the entrainment of rhythms shows different time lag until endogenous response and why the alterations exhibit different crests (DONOVAN, 1 9 7 0 ) . It could also serve as one possible explanation of the persistence of rhythmicity following destruction of the sc. As has been pointed out by MOORE et al. ( 1 9 6 7 , 1 9 6 8 ) , the direct midbrain connection of the AOS could also serve as an information channel to the pineal body. It is generally accepted t h a t this organ in mammals receives photic information and functions as neuroendocrine transducer (OKSCHE and HARTWIG, 1975).

has shown t h a t the depression of serum thyroxin levels after blinding of male golden hamsters could be reversed by removal of either the pineal gland or the superior cervical ganglia. The onset of the circadian pineal function (the pineal NAT rhythm) develops within the first week of life in the rat (ELLISON et al., 1 9 7 2 ) . This coincides with the establishment of synaptic contacts within the sc as well as within the contralateral nit (So et al., VRIEND

(1977)

1977).

E. Photic entrainment of endogen chiasmatic nucleus

rhythmicity

by the

supra-

The circadian rhythms which characterize normal endocrine function are thought to be endogenous and merely synchronized by environmental clues, the most prepotent of which being the daily dark-light cycle ( A D E R , 1 9 7 5 ) . There exist other loci besides the sc responsible for the maintenance of rhythms, located either within the hypothalamus ( K A K O L E W SKI e t a l . , 1 9 7 1 ; N I S H I N O a n d KOIZUMI, 1 9 7 5 ; K A L R A ,

1976) or outside the hypothalamus (see section 2.1., SCHEVING, 1 9 7 6 ) .

Neither the prevention of early environmental exposure to light nor the absence of eyes does infere with the development of any (circadian adrenal-, N A T - , H I O M T - , melatonin-, or locomotor activity-) rhythm which is disturbed after destruction or deafferentiation

of

v . MAYERSBACH,

1.967; K L E I N

the

sc

(ZWEIG et and

al.,

1966;

WELLER,

1970;

RALPH e t al., 1 9 7 1 ; NAGLE e t al., 1 9 7 2 ; FELONG a n d MOORE, 1 9 7 6 ; N I S H I N O e t a l . , 1.976; SILVER,

1.977).

The phases of the free-running periods, however, exhibit variations with characteristic pattern, consistent with the idea of a genetic basis of the rhythms (KONOPKA a n d

BENZER,

1971;

MILLS e t a l . ,

1.975).

The view that the sc is not the "master oscillator" or central rhythm generator as previously ascribed to (MOORE, 1 9 7 4 ; MOORE and K L E I N , 1 9 7 4 ) does not reduce his eminent importance as portal, where environmental photic influences gain access to the

Accessory Optic and Retino-Hypothalamic System

hypothalamus. Recent studies have succeeded in elucidating some cellular dynamics and conduction mechanisms, by which light might influence and synchronize hypothalamic function. Biogenic amine variations are assumed to exert important roles. The exitatory effect of photic stimuli on the sc is well documented ( B R E M E R , 1 9 7 6 ; NISHINO et al., 1 9 7 6 ; S A W A K I , 1 9 7 7 ) . It is suggested that mainly inhibitory neurons are affected. The electrophysiologically observed discharge of sc neurons after retinal-, optic nerve-, or sc stimulation 1 is followed by suppressed firing rate of the superior cervical sympathetic fibres (NCs) (NISHINO et al., 1 9 7 6 ) , thus reducing norepinephrine release at the nerve endings in the pineal gland ( B R O O K S et al., 1 9 7 5 ) . An explanation of the mechanisms by which serotonin influences sc neurons was offered by NISHINO and KOIZUMI ( 1 9 7 7 ) after iontophoretic application of various putative neurotransmitters, including serotonin. They showed that a large proportion of sc neurons which are excited by visual stimuli, are inhibited after the application of serotonin. The involvement of serotonin in the photo-hormonal interaction taking place within the sc is an intriguing problem, since the serotonin content within the in vitro preparation of the sc has observed being subjected to daily variation ( M A Y E R and Q U A Y , 1 9 7 6 ) . It seems not to be synthesized within the sc in appreciable amounts because neither dopamines-hydroxylase, nor tryptophan-hydroxylase showed high activity in the sc under basic (SAAVEDRA, 1 9 7 5 ) , or under experimental conditions ( K I Z E R , 1 9 7 5 ) . It. seems to be derived mainly from the B8-cells of the midbrain raphe, which in turn are possibly directly (FOOTE et al., 1977) or indirectly (CONRAD

and P F A F F , 1 9 7 5 ) activated by visual impulses. These impulses are then transferred via the medial serotonin pathway to the sc and adjacent structures ( G R A N T and S T U M P F , 1 9 7 5 ) . The uptake by the sc serotoninergic terminals is enhanced during the light period. During the dark, the serotonin uptake in vitro by hypothalamic homogenates or slices of the ASC from adult male rats is continuousely reduced ( M E Y E R and Q U A Y , 1 9 7 6 ) whereas the liberation of sertonin from the mesencephalic serotoninergic terminals is increased (HERY et al., 1 9 7 2 ) . The overall elevation of free serotonin within the sc could suppress inhibitory sc activity and thereby release several cell groups (e.g. the pineal body or the preoptic hypnogenic area, BREMER, 1976) from the tonic inhibitory effect of the 1

N I S H I N O et al., gave no precise information about the actual site of sc stimulation. The use of bipolar electrodes suggests they could have stimulated a much larger field than comprised on the sc, including the AOS.

235

sc. Disinhibition of the NCs would cause an increase in norepinephrine release by NCs and thereby augment pineal enzyme and hormone production, such as NAT, HIOMT and melation. Since melatonin is produced by conversion of serotonin, the descreasing content of pineal serotonin during the dark period is possibly reflected by the synchronous decrease of the number of granulated (serotonin containing?) vesicles as observed in mouse pinealocytes ( B E N S O N and KRASOVICH, 1 9 7 7 ; K A C H I , 1 9 7 7 ) . It has been reported that melatonin produces elevated levels of serotonin in the midbrain and hypothalamus, where tritiated melatonin accumulates most heavily ( A N T O N - T A Y , 1 9 7 1 ) . Conversely pinealectomy not only decreases serotonin content of the hypothalamus (MOSZKOWSKA et al., 1 9 7 1 ) but also induces histochemical changes indicating decrease in the number of serotoninergic cells in certain parvicellular nuclei (SMITH and K A P P E R S , 1 9 7 5 ) . The authors suggested that the pineal gland may exert inhibitory control on the neuronal or secretory activity of these nuclei. The mutual relationship between the pineal body and the hypothalamus is also intriguing with regard to some functions of their hormones. It is well known that melatonin has a glandotropic action. Enhancement of the central serotoninergic mechanisms influences or mediates the restrictive effects of the pineal on thyroid ( V R I E N D , 1 9 7 7 ) , adrenocortical (GIORDANO et al., 1 9 7 0 ) , and especially on gonadal function ( W U R T M A N , 1 9 7 5 ) . The inhibitory role of serotonin also includes the action on the GnRH release, possibly involving directly the hormone target cells (see SMITH and K A P P E R S , 1 9 7 5 ) . Intracerebral serotonin application was observed to cause inhibition of the phasic release of L H - R H . Deprivation of hypothalamic serotonin has hardly an effect upon biosynthesis and storage of L H — R H but increases the sensitivity of L H — R H neurones toward neuronal inputs, resulting in a permissive effect on the transmission of cyclic neural inputs activating phasically the release of L H — R H ( s e e SMITH a n d K A P P E R S , 1 9 7 5 ; K O R D O N a n d

RAMI-

In addition, it has been found [in vitro) that a sharply timed and high amplitude increase in serotonin uptake capacity in the ASC (limiting free serotonin and its inhibitory action) occurs at the time during proestrous when the mechanism for stimulation for release of L H is activated LAWSON and GALA, 1 9 7 6 ; M E Y E R and Q U A Y , 1 9 7 6 ) thus indicating participation of sc neurones on the diurnal variation in the sensitivity of the basic L H discharge mechanisms. The suggested role of central serotoninergic mechanisms played at the anterior hypothalamic REZ, 1 9 7 5 ) .

236

Mai, J . K.

("phasic") release regulating center is, certainly, influenced by other neurotransmitters. The dominant components involved in GnRH production and secretion are not yet assessed (see KIZER et al., 1976; LAWSON a n d GALA, 1 9 7 6 ; JOHANSSON, 1976).

Finally, estrogen and progesterone increase brain levels of serotonin (see KIZER, 1975). A single dose of progesterone increased the serotonin uptake in the preoptic area of the rat; in vitro evoked release of 3H-serotonin from rat striatum was diminished by estradiol. It may therefore be suggested that the gonadotropin feedback signals converge at the sc, despite the failure by different experimental methods, to give direct evidence of the involvement of the sc neurons. References P . : Topography of retinal efferent connections in sciurids. Brain Behav. Evol. 9, 3 3 3 - 3 7 5 (1974). ADAM, H . : Discussion at the 53st. Congress of the Anatomical Society at Stockholm 1956. Verhand. Anat. Ges. 53, 147 (1957). A D E L H E I M : Arbeit d. physico-medic. Gesellschaft 261 (1897). (In: N. T U M I A N Z E W (1898). ADER, R . : Neonatal stimulation and maturation of the 24-hour adreno-cortical rhythm. I n : Hormones, homeostasis and the brain. Progr. Brain Res. 42 W. H. Gispen, T j . B . van Wimersma Greidanus, B. Bohns and D. de Wied (Eds.), Elsevier, Amsterdam 3 3 3 - 3 4 1 (1975). A G H A J A N I A N , G. K . , and F . E. B L O O M : Localization of tritiated serotonin in rat brain by electron microscopic autoradiography. J . Pharmacol, exp. Ther. 156, 23 — 30 (1967). A G H A J A N I A N , G. K., F . E. B L O O M and M . H . S H E A R D : Electron microscopy of degeneration within the serotonin pathway of rat brain. Brain Res. 13, 266 — 273 (1969). A K E R T , K . , M . C U E N O D and H . M O O R : Further observations on the enlargement of synaptic vesicles in degenerating optic nerve terminals of the avian optic tectum. Brain Res. 25, 2 5 6 - 2 6 3 (1971). A L E X A N D E R , M . , and H . L I N : Accessory optic fiber system of the golden hamster studied with two silver techniques. Anat. Rec. 184, 574 (1976). A L T M A N , J . : Some fiber projections to the superior colliABPLANALP,

culus in the cat. J . Comp. Neurol. 119, 77 — 97 (1962). J., and D. D. G O P A L : Autoradiographic and histological investigation of changes in the visual system of rats after unilateral enucleation. Anat. Rec. 148, 535 — 545 (1964).

ALTMAN,

ANDEN, N . E . , A . DAHLSTROM, K . ' F U X E , K . LARSSON, L . O L SON and U . U N G E R S T E D T : Ascending monoamine neurons to the telencephalon and diencephalon. Acta physiol. scand. 67, 3 1 3 - 3 2 6 (1966). A N D R E W S , R. V., and E. G. F O L K : Cicardian rhythms in continuous light and darkness: Vertebrates. In: Biology Data Book, Ilnd Ed. Vol. I I Eds. P. L. Altman and D. S. Dittmer. Federation of American Societies for E x perimental Biology, Bethesda, Maryland 1015 — 1018 (1973). A N T O N - T A Y , F . : Pineal-brain relationships. I n : The pineal gland. G. E. W. Wolstenholme and J . Knight (Eds.), A

Ciba Foundation Symposium, Churchill Livingston, London 2 1 3 - 2 2 7 (1971). A N T U N E S - R O D R I G U E S , J., and S. M . M C C A N N : Effect of suprachiasmatic lesions on the regulation of luteinizing hormone secretion in the female rat. Endocrinology 81, 6 6 6 - 6 7 0 (1967). A R I È N S K A P P E R S , C. V. : Die vergleichende Anatomie des Nervensystems der Wirbeltiere und des Menschen. Bd. 2, Bohn, Haarlem 1921. ARIÈNS

KAPPERS,

C. V . ,

G. C. H U B E R

and

E . C. C R O S B Y :

The comparative anatomy of the nervous system of vertebrates including man. Hafner Pubi. Company New York 1936, (reprint 1960). A R M S T R O N G , J . A. : An experimental study of the visual pathways in a reptile (Lacerta vivipara). J . Anat. London 84, 1 4 6 - 1 6 7 (1950). A R M S T R O N G , J . A. : An experimental study of the visual pathways in a snake (Natrix natrix). J . Anat. 85, 275 — 288 (1951). A Z M I T I A , E. C. : Suprachiasmatic nuclei in relation to the reciprocal homeostatic loop between adrenal cortical secretion and tryptophan hydroxylase activity in the brain. Abstr. First European Neurosciences Meeting, Munich, 1 1 - 1 2 (1975). BACH, L. : Experimentelle Untersuchungen und Studien über den Verlauf der Pupillar- und Sehfasern nebst Erörterungen über die Physiologie und Pathologie der Pupillarbewegung. Dt. Zeitschrift für Nervenheilkunde 17, 428 bis 467 (1900). BAN, T. : The septo-preoptic-hypothalamic system and its autonomic function. I n : Correlative Neurosciences. Part A. Fundamental Mechanisms, Progr. Brain Res. 21 A. Eds. T. Tokizane and J . P. Schadé, Elsevier Amsterdam, 1 - 4 3 (1966). BAN, T., T. OKI and K. ZYO: An experimental study on the accessory optic system in the rabbit. Okajimas folia anatomica Japónica 40, 615 — 645 (1965). B A R R A C L O U G H , G . A., and R. A. G O R S K I : Evidence that the hypothalamus is responsible of androgen-induced sterility in the female rat. Endocrinology 68, 68 — 79 (1961). B A R R I S , R. W . , and W . R . I N G R A M : Optic connections of the mid-brain and thalamus. Anat. Rec. 58 Suppl., 3 — 4 (1934). B A R R Y , J . , et G . L E F R A N C : Recherches sur les fibres rétinohypothalamique chez le cobaye. Bull. Ass. Anat. (Nancy) 111, 1 3 2 - 1 4 0 (1962). B A R R Y , J . , M. P. D U B O I S and B . C A R E T T E : Immunofluorescence study of the preoptico-infundibular L R F neurosecretory pathway in the normal, castrated or testosteronetreated male guinea pig. Endocrinology 95, 1416 — 1423 (1974). B A U C H O T , R. : Etude des structures cytoarchitectoniques du diencéphale de Talpa europaea (Insectívora, Talpidae). Acta anat. (Basel) 39, 9 0 - 1 4 0 (1959). B A U M G A R T E N , H. G., and L . L A C H E N M A Y E R : Indoleaminecontaining nerve terminals in the rat median eminence. Z. Zellforsch. 147, 2 8 5 - 2 9 2 (1974). B A U M G A R T E N , H. G. : Quoted according to F . H. Güldner, 1976. B E C C A R I , N. : L a natura del ganglio ottico basale o ectomamillare dell' Edinger, i fasci discendenti genicolare e pretettale ed i loro nuclei interstiziali nei rettili. Monit. Zool. Ital. 33, 7 2 - 7 7 (1922). B E C C A R I , N. : Il centro tegmentale o interstiziale ed altre formazioni poco note nel mesencephalo e nel diencephalo di un rettile. Arch. Ital. di Anat. e di Embr. 20, 560 (1923).

Accessory Optic and Retino-Hypothalamic System N. : Neurologia coraparata. Sansoni Edizioni Scientifiche, Firenze 1943. B E C H E R , H . : Über ein vegetatives, zentralnervöses Kerngebiet in der Netzhaut des Menschen und der Säugetiere. Acta neuroveget. (Wien) 8, 4 2 1 - 4 3 6 (1954). B E C H T E R E W , V. W. : Über den Verlauf der die Pupille verengenden Nervenfasern im Gehirn und über die Localisation eines Centrums für die Iris und Contraction der Augenmuskeln. Pflügers Arch. 31, 60 — 87 (1883a). B E C H T E R E W , V. W. : Die Function der Sehhügel. Experimentelle Untersuchung. Neurol. Centralbl. 2, 7 8 - 8 5 (1883b). B E C H T E R E W , V. W. : Über den Verlauf der die Pupille verengenden Nervenfasern. Neurol. Centralbl. 13, 802 — 807 (1894). B E C H T E R E W , v. W. : Die Leitungsbahnen im Gehirn und Rükkenmark. A. Georgi Verlag Leipzig, Und vol. 1899. B E L L O N I C I , J . : Les lobes optiques des oiseaux. Arch, italiennes de Biologie 4 (1883) (quoted according to W. M. Shanklin, 1933). B E L L O N I C I , J . : Über die zentrale Endigung des Nervus opticus bei den Vertebraten. Zeitschr. für wissensch. Zoologie 47, 1 - 4 6 (1888). B E N O I T , J . , and J . A S S E N M A C H E R : The control by visible radiations of the gonadotropic activity of the duck hypophysis. Recent Progr. Hormone Res. 15, 143 — 164 (1959). B É N O I T , J . : Opto-sexual reflex in the duck: Physiological and histological aspects. Yale J . Biol. Med. 34, 97 — 116 (1961). B E N O I T , J . : The structural components of the hypothalamohypophyseal pathway, with particular reference to the photostimulation of the gonads in birds. Ann. N.Y. Acad. Sei 117, 2 3 - 3 2 (1964a). B E N O I T , J . : The role of the eye and of the hypothalamus in the photostimulation of the gonads in the duck. Ann. N.Y. Acad. Sei 117, 2 0 4 - 2 1 5 (1964b). B E N O I T , J . , and J . A S S E N M A C H E R (Eds.): La photorégulation de la reproduction chez les Oiseaux et les Mammifères. Colloques Internationaux du Centre National de la Recherche Scientifique. No. 172 Paris. Editions du CNRS 1970. B E N S O N , B . , and M. K R A S O V I C H : Circadian rhythm in the number of granulated vesicles in mouse pinealocytes : Effects of denervation or melatonin treatment. Anat. Ree. 187, 536 (1977). B E R K , M. L . , and A. B . B U T L E R : Efferent projections of the preoptic-hypothalamic regions in the pigeon, Columba livia, as demonstrated by the autoradiographic technique. Anat. Ree. 187:537 (1977). BERL, V. : Einiges über Beziehungen der Sehbahnen zu dem vorderen Zweihügel der Kaninchen. Arb. a. d. Neurol. Inst. d. Wien. Univ. 8, 3 0 8 - 3 1 3 (1902). B E R N H E I M E R , S. : Über die Entwicklung und den Verlauf der Markfasern im Chiasma nervosum opticorum des Menschen. J . F. Bergmann, Wiesbaden, 1 - 6 1 (1889). B E R N H E I M E R , S. : Über die Sehnervenwurzeln des Menschen. J . F. Bergmann Wiesbaden 1891. B E R N H E I M E R , S . : Die Reflexbahn der Pupillarreaction. V . Graefe's Archiv f. Ophth. 47, 1 — 49 (1899). BERTHOUD, E . : Développement du nerf optique chez l'embryon de poulet. Arch. Sei. phys. et nat. 5e periode (Genf) 23, 1 8 5 - 1 8 7 (1941). B J Ö R K L U N D , A . , O . L I N D V A L L and A . N O B I N : Evidence of an incertohypothalamic dopamine neurone system in the rat. Brain Res. 89, 2 9 - 4 2 (1975). B L Ü M C K E , S . : Zur Frage einer Nervenfaserverbindung zur Retina und Hypothalamus. I. Anatomische und experiBECCARI,

Hirnforscliung, Bd. 19, Heft 3

237

mentelle Untersuchungen an Meerschweinchen und Katzen. Z. Zellforsch. 48, 2 6 1 - 2 8 2 (1958). B L Ü M C K E , S. : Beitrag zur Frage der Verknüpfung von Retina und Hypothalamus. 56. Verh. Anat. Ges. Zürich 2 2 5 - 2 3 3 (1959). B L Ü M C K E , S. : Vergleichend experimentell-morphologische Untersuchungen zur Frage einer retino-hypothalamischen Bahn bei Huhn, Meerschweinchen und Katze. Z. mikr. anat. Forsch. 67, 4 6 9 - 5 1 3 (1961). B O C H E N E K , A.: Über zentrale Endigungen des Nervus opticus. Anz. Akad. Wiss. Krak. No. 1. Bull, internat. Acad. sc. Cracovie, Classe de sc.-math, et nat. 91 — 95 (1908). B O D I A N , D. : An experimental study of the optic tracts and retinal projection of the Virginia opossum. J . Comp. Neurol. 66, 1 1 3 - 1 4 4 (1937). B O D I A N , D. : Studies on the diencephalon of the Virginia opossum. J. Comp. Neurol. 72, 207 — 297 (1940). B O N S , N., et J . A S S E N M A C H E R : Présence de fibres rétiniennes dégénérées dans la région hypothalamique supraoptique du canard après section d'un nerf optique. C. R. Acad. Sei. (Sér. D.) 269, 1 5 3 5 - 1 5 3 9 (1969). B O N S , N., et I. A S S E N M A C H E R : Nouvelles recherches sur la voie nerveuse rétinohypothalamique chez les oiseaux. C. r. Acad. Sei. 277, 2 5 2 9 - 2 5 3 2 (1973). BONS, N. : Mise en évidence, au microscope électronique, de terminaisons nerveuses d'origine rétinienne dans l'hypothalamus antérieur du canard. C. r. Acad. Sei. 278, 3 1 9 - 3 2 2 (1974). BONS, N. : Retinohypothalamic pathway in the duck (Anas platyrhynchos). Cell Tissue Res. 168, 343 — 360 (1976). B O Y C E , R., and W . B . W A R R I N G T O N : Meeting of the Neurological Society 1897, citet after R. B O Y C E and W . B . W A R RINGTON (1899). B O Y C E , E., and W . B . W A R R I N G T O N : Observations on the anatomy, physiology and degeneration of the nervous system of the bird. Philos. Trans, of the Royal Society, Series B, 191, 2 9 3 - 3 0 5 () 305) (1899). B R A U T H , S. E., and H. J . K A R T E N : Direct accessory optic projections to the vestibulo-cerebellum : A possible channel for oculomotor control systems. Exp. Brain Res. 28, 7 3 - 8 4 (1977). B R E M E R , F. : Photic responses of the basal preoptic area in the cat. Brain Res. 115, 1 4 5 - 1 4 9 (1976). B R O C K H A U S , H. : Beitrag zur normalen Anatomie des Hypothalamus und der Zona incerta beim Menschen. J . Psychol, u. Neur. 51, 9 6 - 1 9 6 (1942). B R O O K S , C. M., T. I S H I K A W A and K . K O I Z U M I : Autonomie system control of the pineal gland and the role of this complex in the integration of body function. Brain Res. 87, 1 8 1 - 1 9 0 (1975). B R O U W E R , B . , und W. P. C. Z E E M A N : Experimentell-anatomische Untersuchungen über die Projektion der Retina auf die primären Opticuszentren. Schweiz. Arch. f. Neurol, u. Psychiat. 13, 1 1 8 - 1 3 7 (1923). BROUWER, B.,

W . P . C. ZEEMAN

and

A. W . M.

HOUWER:

The projection of the retina in primary optic neuron in monkeys. Brain Res. 49, 1 - 3 5 (1926). B R U G I , G. : Reperti istologici sperimentali nel polio a conferma dell' esistenza di dirette connessioni del tratto ottico con la zona anteriore dell'ipotalamo. Monit. Zool. Ital. 48, 2 6 4 - 2 6 8 (1937). B Ü N N I N G , E. : The physiological clock. The Heidelberg Science Library, Vol. I, Und ed. Springer Verlag Berlin, Heidelberg, New York 1967. B U R N S , A. N., and D. C. GOODMAN: Retino-fugal projec17

238 Mai,

J.

K.

tions of Caiman sklerops. Exp. Neurol. 18, 105 — 115 (1967). B U T L E R , J . E., and B . T . D O N O V A N : Consequences of hypothalamic deafferentiation in female rats and guinea pigs. J . Endocrin. 43 (Suppl.) p. X X (1969). B U T L E R , B . , and R. G . N O R T H C U T T : Retinal projections in Iguana iguana and Anolis carolinensis. Brain Res. 26, 1 - 1 3 (1971). C A I R N E Y , J . : A general survey of the forebrain of Sphenodon punctatum. J . Comp. Neurol. 42, 2 5 5 - 3 4 8 (1926). C A M P B E L L , C . B. G.: The visual system of insectivores and primates. Ann. N. Y. Acad. Science 167, 3 8 8 - 4 0 3 (1969). C A M P B E L L , C . B. G., J . A. J A N E and D. Y A S H O N : The retinal projections of the tree-shrew and hedgehog. Brain Res. 5, 4 0 6 - 4 1 8 (1967). C A M P B E L L , C . B. G., and S . . O. E . E B B E S S O N : The optic system of a teleost: Holocentrus, reexamined. Brain Behav. Evol. 2, 4 1 5 - 4 3 0 (1969). C A M P B E L L , C. B . G . , and W . R . H A Y H O W : Primary optic pathways in the echidna, Tachyglossus aculeatus. An experimental degeneration study. J . Comp. Neurol. 143, 1 1 9 - 1 3 6 (1971). C A M P B E L L , C . B . G . , and W . R . H A Y H O W : Primary optic pathways in the duckbill platypus, Ornithorynchus anatinus: an experimental degeneration study. J . comp. Neurol. 145, 1 9 5 - 2 0 8 (1972). C A M P B E L L , C . B . G . , and J . A . R A M A L E Y : Retinohypothalamic projections: Correlations with onset of the adrenal rhythm in infant rats. Endocrinology 25,1201 —1204(1974). CAMPBELL, W . B . ,

S. N. BROOKS

and

W . A.

PETTINGER:

Angiotensin II- and angiotensin Ill-induced altosterone release in vivo in the rat. Science 184, 994 — 996 (1974).

CAMPBELL, W . B . ,

W . A. PETTINGER,

K . KEETON and S. N.

Vasodilatating antihypertensive drug-induced aldosterone release. A study of endgenous angiotensine — mediated aldosterone release in the rat. J . Pharmacol. Exper. Therap. 193, 1 6 6 - 1 7 5 (1975). C A M P O S - O R T E G A , J . A . : The distribution of retinal fibers in the brain of the pig. Brain Res. 19, 3 0 6 - 3 1 2 (1970). CAMPOS-ORTEGA, J . A., and P . G L E E S : The subcortical distribution of the optic fibers in Saimiri sciureus (Squirrel monlcey). J . Comp. Neurol. 131, 1 3 1 - 1 4 2 (1967). C A M P O S - O R T E G A , J . A . , and P . F. C L U V E R : The distribution of retinal fibers in Galago crassicaudatus. Brain Res. 7, 4 8 7 - 4 8 9 (1968). C A R P E N T E R , M . B . , and R . J . P I E R S O N : Pretectal region and the pupillary light reflex. An anatomical analysis in the monkey. J . Comp. Neur. 149, 271 -300-(1973). CASAGRANDE, V . A . , and J . K . H A R T I N G : Transneuronal transport of tritiated fucose and proline in the visual pathways of tree shrew Tupaia glis. Brain Res. 96, 367 — 372 (1975). C A S T A L D I , L . : Studi sulla struttura e sullo sviluppo del mesencephalo. Ricerche in Cavia cobaya, I. Arch. Ital. di Anat. e di Embriol. 20, 2 3 - 2 2 5 (1923). BROOKS:

CAVALCANTE, L . A . ,

C. E . ROCHA-MIRANDA

and

R.

LENT:

Hypothalamic tectal and accessory optic projections in the opossum. Brain Res. 84, 302 — 307 (1975). C H A N G , H . T . : The primary connections of the optic nerve of the albino rat. Chin. Journal of Zoology 11, 17 (1936). C H A P P E L , S. C . , and C . A . B A R R A C L O U G H : Hypothalamic regulation of pituitary FSH secretion. Endocrinology 98, 9 2 7 - 9 3 5 (1976). CHOMIAK, M . ,

Z. MILART,

S. SZTEYN

and

J.WELENTO:

Experimental investigation on the visual centres in the sheep. J . Hirnforsch. 11, 3 6 7 - 3 7 5 (1969).

CHU, H.-N. : The cell masses of the diencephalon of the Opossum, Didelphis virg. Monographs of the National Res. Inst, of Psychol. 2, 1 - 3 7 (1932). CHU, H.-N. : The fiber connections of the diencephalon of the Opossum, Didelphis virg. Monographs of the National Res. Inst, of Psychol. 3, 1 - 4 6 (1932). C L A R A , M. : Das Nervensystem des Menschen. Barth-Verlag, Leipzig 3rd ed. 1959. CLATTENBURG, R . E . ,

R . P . SINGH a n d D . G . MONTEMURRO:

Ultrastructural changes in the preoptic nucleus of the rabbit following coitus Neuroendocrinology 8, 289 — 306 (1971).

CLATTENBURG, R . E . , R . P . SINGH a n d D . G . MONTEMURRO:

Post-coital ultrastructural changes in neurons of the suprachiasmatic nucleus of the rabbit. Z. Zellforsch. Mikrosk. Anat. 125, 4 4 8 - 4 5 9 (1972).

CLATTENBURG, R . E . , D . G . MONTEMURRO a n d J . E .

BRUNI:

Neurosecretory activity within suprachiasmatic neurons of the female rabbit following castration. Neuroendocrinol. 17, 2 1 1 - 2 2 4 (1975).

CLATTENBURG, R . E . ,

J . F . ORANGE, J . E . B R U N I a n d D . G.

Suprachiasmatic (SCH) neurons: Morphological changes and mean serum lueinizing hormone (LH) levels in the female rat. Anat. Ree. 184, 379 (1976). COLLENZA, D . : Contributo sperimentale alio studio dei rapporti fra via ottica e commissure sopraottiche. Monit. Zool. ital. 4, 6 0 - 6 3 (1943) (cited in: J . Repérant, 1973). C O L L I N , R. : Sur l'existence probable d'une voie reflexe courte opto-hypothalamo-pituitaire. C.R. Soc. Biol. (Paris) 118, 1 5 6 0 - 1 5 6 2 (1935). C O N R A D , C . D., and W. C. S T U M P F : Retinal projections traced with thaw-mount autoradiography and multiple injections of tritiated precusor or precusor coctails. Cell. Tiss. Res. 155, 2 8 3 - 2 9 0 (1974). Direct visual input C O N R A D , C . D., and W. E. S T U M P F : to the limbic system: Crossed retinal projections to the nucleus anterodorsalis thalami in the Tree shrew. Exp. Brain Res. 23, 1 4 1 - 1 4 9 (1975). C O N R A D , C. D., and W. E. S T U M P F : Endocrine-optic pathways to the hypothalamus. Anat. Neuroendocrinology. Int. Conf. Neurobiology of CNS-Hormone Interactions, Chapel Hill 1 5 - 2 9 , 1974 (Karger, Basel 1975). C O N R A D , L . C . A. and D . W . P F A F F : Axonal projections of medial preoptic and anterior hypothalamic neurons. Science 190, 1112-1114 (1975). C O W A N , W. M., L. Adamson and T. P . S. P O W E L L : An experimental study of the avian visual system. J . Anat. (Load.) 95, 5 4 5 - 5 6 3 (1961). C R A I G I E , E. H.: Observations on the brain of the humming bird (Chrysolampis mosquitus Linn and Chlorostilbon caribaeus Lawr.). J . Comp. Neurol. 45, 377 — 481 (1928). C R I T C H L O W , V. : The role of light in the neurosecretory system. In: Advances in Neuroendocrinology. Ed. A. V. Nalbandov Univ. Illinois Press, Urbana 111, 377 — 402 (1963). C R I T C H L O W , V . , and J . D E G R O O T : Experimental investigations of pathways involved in light-induced constant . estrous in the rat. Anat. Ree. 136, 179 (1960). C R O S B Y , E. C . , and E. W. L A U E R : Anatomy of the midbrain. IN: Einführung in die stereotaktischen Operationen. Hrsg. G. Schaltenbrand and P. Bailey I 88 — 118 G. Thieme Verlag Stuttgart 1959. C R O S B Y , E. C . , and M. J . C . S H O W E R S : Comparative anatomy of the preoptic ad hypothalamic areas. IN: The Hypothalamus. Eds. : W. Haymaker, E. Anderson and W. J . H. Nauta. Ch. C. Thomas Publ. Springfield, Illinois, USA, 6 1 - 1 3 5 (1969). MONTEMURRO:

Accessory Optic and Retino-Hypothalamic System CUÉNOD, M . ,

J . BOESCH,

P . MARKO,

M. PERISIC,

C. SANDRI

and J . S C H O N B A C H : Contributions of axoplasmic transport to synaptic structures and functions. Intern. J . Neuroscience 4, 77 — 87 (1972). C U M M I N G S , J . F., and Y . D E L A H U N T A : An experimental study of the retinal projections in the horse and sheep. Ann. N.Y. Acad. Sei. 167, 2 9 3 - 3 1 8 (1969). C U N N I N G H A M , T. J., and M. A. S E G R A V E S : Cobalt filling of bilateral ganglion cell branches in the rat. Normal and expanded retinal projections. Anat. Ree. 184, 386 (1976). C Y B U L S K I , G. R., and E. K I C L I T E R : Retinal projections in the puppy, Necturus maculosus. Anat. Ree. 184, 386 to 387 (1976). D A H L S T R Ö M , A., and K . F U X E : Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, 1 - 5 5 (1964). D A R K S C H E W I T S C H , L . : Über die sogenannten primären Opticuscentren und ihre Beziehung zur Großhirnrinde. Archiv f. Anat. und Physiol. Anat. Abt. 10, 2 4 9 - 2 7 0 (1886a). D A R K S C H E W I T S C H , L . : Einige Bemerkungen über den Faserverlauf in der hinteren Commissur des Gehirns. Neurol. Centralbl. 5, 9 9 - 1 0 3 (1886b). D A R K S C H E W I T S C H , L . : Über die Pupillenfasern des Tractus opticus. Wratsch 43 (1886c) (cited in: Neurol. Centraiblatt 6, 36 (1887). D A R K S C H E W I T S C H , L. : Über die Leiter der Lichtreizung von der Netzhaut auf den Oculomotorius (russ.) Moskau 1887 (according to: Tümianzew, N. 1898). D E L A N G E , S . J . : Das Zwischenhirn und das Mittelhirn der Reptilien. Folia Neurobiol. 7, 6 7 - 1 3 8 (1913). D E L M A S , J . : Les centres autonomes diencéphaliques. Montpellier Medical 43, 1 9 5 - 2 4 6 (1953). D E R E N Z I , C . , F . M A G N I , G . F . Rossi and P . S T R A T A : Optic projections to the brain stem tegmentum in the mouse. Arch. Ital. Biol. 97, 1 5 6 - 1 6 6 (1959). DIEPEN, R.,

P.JANSSEN,

F.ENGELHARDT

and

H.SPATZ:

Recherches sur le cerveau de l'éléphant d'Afrique (Loxodonta africana Blum) II. Données sur l'hypothalamus. Acta Neurol, Belgica 11, 7 5 9 - 7 8 7 (1956). D I E P E N , R . : Der Hypothalamus. In: Handb. der Mikrosk. Anat. des Menschen. Hrsg. W. v. Möllendorf and W. Bargmann 4 (7) 1 — 525 Springer Verlag Berlin, Göttingen, Heidelberg (1962). Di V I R G I L I O , G . , N. L A V E N D A and G . F. G E S T R I N G : Optic connections of the hypothalamus in mammals studied by a silver technique. Anat. Ree. 131, 546 (1958). D I V I R G I L I O , G . , N . L A V E N D A and G . F . G E S T R I N G : Proof of retinal representation in the hypothalamus: A preliminary communication with two illustrations. Acta Ophthal. (Kopenhagen) 42, 9 3 9 - 9 5 0 (1964). D O G I E L , A. S. : Ein besonderer Typus von Nervenzellen in der mittleren gangliösen Schicht der Vogel-Retina. Anat. Anz. 10, 7 5 0 - 7 6 0 (1895). D O L L A N D E R , A . : La voie nerveuse opto-tangentielle directe chez le Cobaye. Thesis, Nancy 1947. D O N A T E L L I , L . : Su di un fascio di fibre mieliniche decorrente nella lamina terminale degli uccelli. Neopsichiatrica 1, 58 (1935) (cited in: Beccari, N. 1943). D O N A T E L L I , L. : Contributo alla conoscenza delle commessure sopraottiche I. Rapporti ira vie ottiche e commessure sopraottiche negli uccelli. Rassegna di studi psichiatrici 25, 27 (1936). (cited in: Beccari, N. 1943). D O N O V A N , B. T. : The regulation of the secretion of folliclestimulating hormone. In: The pituitary gland. Eds.

239

G. W. Harris and B. T. Donovan. Butterworths, London 2, 4 9 - 9 8 (1966). D O N O V A N , B. T . : Mammalian Neuroendocrinology. McGrawHill Publ. Comp. London (1970). D R Ä G E R , V. C.: Autoradiography of tritiated proline and fucose transported transneuronally from the eye to the visual cortex in pigmented and albino mice. Brain Res. 82, 2 8 4 - 2 9 2 (1974). D R A G E R , G. A., and C. A. B A K E R : Anatomical investigation of retino-pituitary reflex. Tex. Rep. Biol. Med. 2, 4 0 1 - 4 0 4 (1944). DYER, R . G.,

R. B. J . DYBALL

and

J.F.MORRIS:

The

effect of hypothalamic deafferentiation upon the ultrastructure and hormone content of the paraventricular nucleus. J . Endocrinol. 57, 509 — 516 (1973).

D Y E R , R . S.,

M . F . MARINO,

C. JOHNSON

and

T.

KRUGGEL:

Superior colliculus lesions do not impair orientation to pattern. Brain Res. 112, 1 7 6 - 1 7 9 (1976). E B B E S S O N , S. O. E . : Retinal projections in two teleost fishes. Brain Behav. Evol. 1, 134 — 154 (1968). E B B E S S O N , S. O. E . : On the organization of central visual pathways in vertebrates. Brain Behav. Evol. 3, 178 — 194 (1970). E B B E S S O N , S. O. E . : A proposal for a common nomenclature for some optic nuclei in vertebrates and the evidence for a common origin of two such cell groups. Brain Behav. Evol. 6, 7 5 - 9 1 (1972). E B B E S S O N , S. O. E . , and J . S. R A M S E Y : The optic tracts of two species oi sharks. Brain Res. 8, 36 — 53 (1968). E B B E S S O N , S . O. E . , and D. M. S C H R O E D E R : Connections of the nurse shark's telencephalon. Science 173, 254—256 (1971). EBBESSON, S. O. E . ,

S. RIDGEWAY

and

P. M. FULLER:

A

note on the .retinal projections in the western gull. (1972) (cited in: S. O. E. Ebbeson, 1972). E D I N G E R , L . : Vorlesungen über den Bau der nervösen Centraiorgane der Tiere und des Menschen. F. C. W. Vogel, Leipzig. 1. Ed. 1885, 2. Ed. 1889, 5. Ed. 1896, 6. Ed. 1905, 7. Ed. 1908, 8. Ed. 1911. E D I N G E R , L.: Untersuchungen über die vergleichende Anatomie des Gehirns. I. Das Vorderhirn. Abh. d. Senckenbergischen Naturforsch. Ges. Frankfurt/M. 15, 91 — 121 (1888).

L . : Das Zwischenhirn. 1. Teil: Das Zwischenhirn der Selachier und Amphibien. Abhandlungen der Senckenberg. Naturforschenden Gesellschaft 18, 1 — 55 (1892). E D I N G E R , L.: Vorlesungen über den Bau der nervösen Centraiorgane der Tiere und des Menschen. 5th ed. Leipzig 1896, 8. Auflage 1911 (Vol. II). E D I N G E R , L.: Untersuchungen über die vergleichende Anatomie des Gehirns. 4. Studien über das Zwischenhirn der Reptilien. Abhandlungen der Senckenberg. Naturforschenden Gesellschaft 20, 161 — 197 (1899). E D I N G E R , L . , und A. W A L L E N B E R G : Untersuchungen über das Gehirn der Tauben. Anat. Anz. 15, 2 4 5 - 2 7 1 (1899). E I C H L E R , V. B., and R. Y. M O O R E : The primary and accessory optic systems in the golden hamster, Mesocricetus auratus. Acta Anat. (Basel) 89, 359 — 371 (1974). EDINGER,

EDWARDS, S. B . ,

A . C. ROSENQUIST

and

L. A. PALMER:

An

autoradiographic study of ventral lateral geniculate projections in the cat. Brain Res. 72, 282 — 287 (1974). E L L I S S O N , N., J . L . W E L L E R and D. C . K L E I N : Development of a circadian rhythm in the activity of pineal serotonin N-acetyltransferase. J . Neurochem. 19, 1 3 3 5 - 1 3 4 1 (1972). E V E R E T T , J . W . , and H . M . R A D F O R D : Irritative deposits 17*

240

Mai, J. K.

from stainless steel electrodes in the preoptic r a t brain causing release of pituitary gonadotropin. Proc. Soc. Exptl. Biol. Med. 108, 6 0 4 - 6 0 9 (1961). EVERETT, E . W . ,

H.M.RADFORD

and

J. HOLSINGER:

In:

and A. P E C I L E (Eds.), Hormonal Steroids, Pharmacology and Therapeutics, Proceedings of t h e first International Congr. on Hor. Steroids, Vol. I, Academic Press, New York, 285 (1965). E V E R E T T , J. W., D. L. Q U I N N and L. T Y R E Y : Comparative effectiveness of preoptic and tuberai stimulation for luteinizing hormone release and ovulation in two strains of rats. Endocrinology 98, 1 3 0 2 - 1 3 0 8 (1976). F A R N E R , D. S., R . A . L E W I S and T. R . D A R D E N : Photoperiodic control mechanisms: Homoiothermic animals. I n : Biology D a t a Book, U n d Ed. Vol. II, Eds. P. L. Altman and D. S. Dittmer, Federation of American Societies for Experimental Biology, Bethesda, Maryland 1973. F E L D M A N , S . : Visual projections to the hypothalamus and preoptic area. Ann. N.Y. Acad. Sci. 117, 5 3 - 6 6 (1964). F E L O N G , M . : Development of retinohypothalamic projection in the rat. Anat. Ree. 184, 400 — 401 (1976). F E L O N G , M . , and R . Y . M O O R E : Development of a circadian r h y t h m in pineal N-acetyltransferase in the rat. Neurosci. Abstr. 2, 670 (1976). MARTINI, L.,

FERIN, M.,

P . W . CARMEL,

E . A . ZIMMERMAN,

M.

WARREN,

and R . L. V A N D E W I E L E : Location of intrahypothalamic estrogen-responsive sites influencing L H secretion in the female rhesus monkey. Endocrinology 95, 1 0 5 9 - 1 0 6 8 (1974). F I T E , K. V., and F. S C A L I A : Central visual pathways in t h e frog. In : The amphibian visual system Ed. : K. V. Fite, Academic Press, New York 87 — 118 (1976). F L A M E N T - D U R A N D , J . : Contribution à l'étude des relations hypothalamo-hypophysaires. Ann. Soc. roy. Sei. med. nat. Brüx. 19, 8 8 - 9 9 (1966). F L E C H S I G , P. : Zur Lehre vom centralen Verlauf der Sinnesnerven. Neurolog. Centralblatt 5, 545 — 551 (1886). F L E C H S I G , P . : Sitzung der m a t h e m . physikal. Classe der Königlich Sachs. Gesellschaft der Wissenschaften 1886 (cited in : Bogrow). F o i x , C . , et L. N I C O L E S C O : Anatomie cérébrale. Les noyaux gris centraux et la région mésencéphalo-sous-optique Masson, Paris 1925. R. PEREZ

FOOTE, W . E., E . TABER PIERCE a n d

D. L. EDWARDS:

Pro-

jections from the retina to t h e nucleus raphe dorsalis in the c a t : an autoradiographic study. Anat. Ree. 187, 580 (1977). F O R E L , A.: Cited according t o B. v. Gudden (1881). F R A N K L - H O C H W A R T , L . V . : Zur Kenntnis der Anatomie des Gehirns der Blindmaus (Spalax typhlus). Arbeiten aus dem Neurologischen I n s t i t u t der Universität Wien. 8, 1 9 0 - 2 2 0 (1902). F R E D E R I K S E , A.: Inaugural Diss. Amsterdam 1 9 3 1 . FREY, E. : Die basale optische Wurzel des Meerschweinchens. Proc. Roy. Acad. Amsterd. 38, 7 7 5 - 7 8 3 (1935). FREY, E . : 4. Vergleichend-anatomische Untersuchungen über die basale optische Wurzel, die Commissura transversa Gudden und über eine Verbindung der N e t z h a u t mit dem vegetativen Gebiet im H y p o t h a l a m u s durch eine „dorsale hypothalamische Wurzel" des Nervus opticus bei Amnioten. P a r t I : Schweizer Arch. Neurol. Psychiat. 39, 2 5 5 - 2 9 0 (1937). P a r t I I : Schweizer Arch. Neurol. Psychiat. 40, 6 9 - 1 2 6 (1938). F R E Y , E . : Studien über die hypothalamische Opticuswurzel der Amphibien. Proc. Roy. Acad. Amsterd. ,41, 1004 — 1021 (1938).

FREY, E. : Studien über die Entwicklung der zentralen optischen Bahnen des Menschen. I. Die Entwicklung des Opticus und des Chiasma opticum. Schweizer Arch. Neurol. Psychiat. 47, 74 — 124 (1941). FREY, E. : Degenerationsstudien über das optische Gebiet im H y p o t h a l a m u s des Meerschweinchens. Acta Anat. 4, 1 2 3 - 1 3 6 (1947). FREY, E. : Neue anatomische und experimentelle Ergebnisse über das optische System des Hypothalamus. Schweiz. Arch. Neurol. Psychiat. 66, 67 — 86 (1950). FREY, E. : Über die hypothalamische Opticuswurzel des Hundes. Bull. Schweiz. Acad. Med. Wiss. 7, 115 — 127 (1951). FREY, E. : Neue anatomische Ergebnisse zur Phylogenie der Sehfunktion. Bücherei des Augenarztes 22, 45 — 94 (1955). F R I E D E M A N N , M. : Die Cytoarchitectonic des Zwischenhirns des Cercopitheken m i t besonderer Berücksichtigung des Thalamus opticus. J. f. Psychiol. u. Neurol. 18, Ergänzungsheft 2, 3 0 9 - 3 7 8 (1912). F U L L E R , P . M., and D. J . P R I O R : Cobalt iontophoresis techniques for tracing afferent and efferent connections in t h e vertebrate CNS. Brain Res. 88, 2 1 1 - 2 2 0 (1975). FUXE, K. : The distribution of monoamine terminals in t h e central nervous system of the rat. Acta physiol. scand. 64, Suppl. 247 (1965). F U X E , K., and T. H Ö K F E L T : Catecholamines in t h e hypothalamus and the pituitary gland. In : Frontiers in Neuroendocrinology. Eds. : W. F. Ganong and L. Martini. Oxford University Press, London 47 — 96 (1969). G A L L , F. J., and G . S P U R Z H E I M : Anatomie et physiologie du système nerveux en general et du cerveau en particulier, (Atlas), Paris 1810. I n : Anatomie et physiologie du système nerveux. Schoell, Paris 1825. G A N S E R , S.: Über die periphere und centrale Anordnung der Sehnervenfasern und über das Corpus bigeminum anterius. Arch. f. Psych, und Nervenkrank. 13, Vol. 2, 3 7 4 - 4 8 1 (1882). G A R E Y , L. J . , and T. S. P . P O W E L L : The projection of t h e retina in t h e cat. J. Anat. (Lond.) 102, 1 8 9 - 2 2 2 (1968). G A R R I S , D. R . , and J . A. M I T C H E L L : Direct septo-hypothalamic projections in t h e r a t : An autoradiographic study. Neuroscience Abstracts, Vol. II, P a r t 1, Society for Neuroscience sixth Annual Meeting, Toronto, Canada 1976. G A U P P , E. : Anatomie des Frosches. 3. Aufl. Vieweg & Sohn, Braunschweig 1896. Abt. II, 2. Aufl., Vieweg & Sohn, Braunschweig 1899. G E H U C H T E N V A N , A. : Anatomie du système nerveux de l'homme. 4 ed. Louvain 1906. G E I R I N G E R , M. : Die Beziehungen der basalen Opticuswurzel zur Hypophyse und ihre Bedeutung f ü r den Farbwechsel der Amphibien. Anat. Anz. 86, 202 — 207 (1938). GERARD, R . W . , H.W.MARSHALL and L . J . S A U L : Electrical activity of t h e cat's brain. A. M. A. Arch. Neurol. Psychiat. 36, 6 7 5 - 7 3 8 (1936). G E R G E N , J. A., and P. D. M A C L E A N : The limbic system: Photic activation of limbic cortical areas in the squirrel monkey. Ann. N.Y. Acad. Sei. 117, 6 9 - 8 7 (1964). GHETTI, B.,

D . S. HOROUPIAN

and

H . M. WISNIEWSKI :

Transsynaptic response of the lateral geniculate nucleus and the p a t t e r n of degeneration of t h e nerve terminal in the rhesus monkey after eye enucleation. Brain Res. 45, 3 1 - 4 8 (1972). G I L L I L A N , L. A., and M. E. W O O L L E Y : The connections of t h e nucleus of t h e basal optic root in various mammals. Anat. Ree. 73, Suppl. 2 1 - 2 2 (1939).

Accessory Optic and Retino-Hypothalamic System GILLILAN, L. A. : The connections of the basal optic root (posterior accessory optic tract) and its nucleus in various mammals. J. Comp. Neurol. 74, 3 6 7 - 4 0 7 (1941). GIOLLI, R . A. : Experimental study of the anterior and posterior accessory optic tracts in the rabbit. Anat. Ree. 136, 336 (1960). GIOLLI, R. A.: An experimental study of the accessory optic tracts (transpeduncular tract and ant. acc. optic tracts) in the rabbit. J . Comp. Neur. 117, 7 7 - 9 5 (1961). GIOLLI, R. A. : An experimental study of the accessory optic system in the Cynomolgus monkey. J. Comp. Neurol. 121, 8 9 - 1 0 7 (1963). GIOLLI, R. A. : An experimental study of the accessory optic system and of other optic fibers in the opossum, Didelphis virginiana. J . Comp. Neurol. 124, 2 2 9 - 2 4 2 (1965). GIOLLI, R . A . ,

J . R . BRAITHWAITE

and

T. T.

STREETER:

Golgi-study of the nucleus of the transpeduncular tract in the rabbit. J . Comp. Neurol. 133, 3 0 9 - 3 2 8 (1968). GIOLLI, R . A . ,

and

M . D . GUTHRIE:

The

primary

optic

projections in the rabbit. An experimental degeneration study. J . Comp. Neurol. 136, 9 9 - 1 2 5 (1969). GIOLLI, R. A., and J . TIGGES: The primary optic pathways and nuclei of primates. I n : The primate brain. Eds. Noback and Montagna 29 — 54 (Appleton-Century-Crofts, New York 1970). GIOLLI, R . A., a n d J . E . POPE: T h e a n a t o m i c a l o r g a n i z a t i o n

of the visual system of the rabbit. Doc. Ophthalmol. 30, 9 - 3 1 (1971). GIOLLI, R . A., and D. J . CREEL: The primary optic projections in pigmented and albino guinea pigs : An experimental degeneration study. Brain Res. 55, 25 — 39 (1973). GIORDANO, G . , R . B A L E S T R E R I ,

G . E . JACOPINO,

E.FOPPIANI

and S. BERTOLINI: L'action in vitro de la mélatonine sur l'hormonosynthèse corticosurrénale du rat. Ann. Endocrin., Paris 31, 1 0 7 1 - 1 0 8 0 (1970). GOLDBERG, S., and M. KOT ANI: The projection of optic nerve fibers in the frog R a n a catesbeiana as studied by radioautography. Anat. Ree. 158, 3 2 5 - 3 3 2 (1967). GOLDSTEIN, K . : Untersuchungen über das Vorderhirn und Zwischenhirn einiger Knochenfische. Arch. mikr. Anat. 66, 1 4 - 2 6 (1905). GORSKI, R . ,

J . SHRYNE,

J . GORDON

and

L . CHRISTENSEN :

Evidence for a morphological sex difference within the medial preoptic area (MPOA) of the rat. Anat. Ree. 187, 591 (1977). GRAEBER, R . C.,

and

S . O. E . EBBESSON :

Retinal

projec-

tions in the lemon shark (Negaprion brevirostris). Brain Behav. Evol. 4 6 1 - 4 7 7 (1972). GRANT, L. D., and W. E . STUMPF: Hormone uptake sites in relation to CNS biogenic amine systems. I n : Anatomical Neuroendocrinology Int. Conf. Neurobiology of CNSHormone Interactions, Chapel Hill 445 — 463 (1974). (Karger, Basel, 1975). GRAY, E . G., a n d L . H . HAMLYN: E l e c t r o n

microscopy

of

experimental degeneration in the avian optic tectum. J . Anat. (Lond.) 96, 3 0 9 - 3 1 6 (1962). GRAYBIEL, A. M. : Visuo-cerebellar and cerebello-visual connections involving the ventral lateral geniculate nucleus. E x p . Brain Res. 20, 303 — 306 (1974). GREVING, R. : Beiträge zur Anatomie der Hypophyse und ihrer Funktion. I. Eine Faserverbindung zwischen Hypophyse und Zwischenhirnbasis (Tr. supraoptico-hypophyseus). Deutsch. Zeitschr. Nervenheilk. 89, 179 — 195 (1926). GREVING, R . : Die zentralen Anteile des vegetativen Nervensystems. 4. Die Fasersysteme des Hypothalamus. I n :

241

Von Möllerdorff's Hbd. d. mikr. Anat. d. Menschen. Springer Verlag Berlin. Vol. IV, part 1, 1 0 1 2 - 1 0 3 7 (1928). GRIZZLE, W . E . ,

M . F . DALLMAN,

L . P . SCHRAMM a n d

D . S.

GANN: Inhibitory and facilitatory hypothalamic areas mediating ACTH release in the cat. Endocrinology 95, 1 4 5 0 - 1 4 6 1 (1974). GROEBBELS, F . : Untersuchungen über den Thalamus und das Mittelhirn der Vögel. Anat. Anz. 57, 385 — 415 (1924). GROSS, D . S . : Distribution of gonadotropin-releasing hormone in the mouse brain as revealed by immunhistochemistry. Endocrinology 98, 1 4 0 8 - 1 4 1 7 (1976). GRUBERG, E . R . ,

a n d G. A. GREENHOUSE:

The

relationship

of acetylcholinesterase activity to optic fiber projections in the tiger salamander Amblystoma tigrinum. J . Morphol. 141, 1 4 7 - 1 5 6 (1973). GRÜNTHAL, E . : Vergleichend anatomische und entwicklungsgeschichtliche Untersuchungen über die Zentren des Hypothalamus der Säuger und des Menschen. Arch. Psychiat. 90, 2 1 6 - 2 6 7 (1930). GRÜSSER-CORNEHLS, U . ,

and

W . HIMSTEDT:

The

Urodele

visual system. I n : The amphibian visual system. A multidisciplinary approach. E d . : K . V . . F i t e , Academic Press, New York, 2 0 3 - 2 6 6 (1976). GUDDEN, B . V. : Über einen früher nicht beschriebenen Nervenfaserstrang im Gehirn der Säugetiere und des Menschen. Arch. f. Psychiat. 2, 3 6 4 - 3 6 6 (1870a). GUDDEN, V. B . : Experimentaluntersuchungen über das peripherische und centrale Nervensystem. Arch. f. Psychiat. 2, 6 9 3 - 7 2 3 (1870b). GUDDEN, B . V. : Über den tractus peduneularis transversus. Arch. f. Psych. 11, 4 1 5 - 4 2 3 (1881). GUDDEN, B . v . : Versammlung der deutschen Naturforscher und Ärzte in Straßburg vom 18. —25. Sept. 1885 (in: N. Tümianzew, 1898). GUDDEN, V. B . : Gesammelte und hinterlassene. Abhandlungen. J . F . Bergmann, Wiesbaden (1889). GÜLDNER, F . H . ,

and

J. R. WOLFF:

Dendro-dendritic

syn-

apses in the suprachiasmatic nucleus of the rat hypothalamus. J . Neurocytol. 3, 2 4 5 - 2 5 0 (1974). GÜLDNER, F . H . : Synaptology of the rat suprachiasmatic nucleus. Cell. Tiss. Res. 165, 5 0 9 - 5 4 4 (1976). GUILLERY, R . W . ,

and

B . V . UPDYKE:

Retinofugal

path-

ways in normal and albino axolotl. Brain Res. 109, 2 3 5 - 2 4 4 (1976). GUPTA, K . C.: The afferent connections of the nucleus ventromedialis hypothalami of the cat. Anat. Ree. 184, 418 (1976). GURDJIAN, E . S . : The diencephalon of the albino rat. J . Comp. Neurol. 43, 1 - 1 1 4 (1927). HAGUE, E . B . : Photo-neuro-endocrine effects in circadian systems with particular reference to the eye. Ann. N.Y. Acad. Sei. 1964. HALÄSZ, B . ,

L . PUPP

and

S. UHLARIK:

Hypophysiotrophic

area in the hypothalamus. J . Endocrin. 25, 147 — 154 (1962). HALÄSZ, B . : Endocrine function of hypothalamic islands. I n : Progress in Endocrinology. Excerpta Medica Foundation, Amsterdam. Int. Congress Series 184, 508 — 514 (1969). HAMASAKI, D . , a n d E . MARG: A n h i s t o r i c a l r e v i e w of

accessory optic tracts. (1960a).

Amer.

J.

Optom.

37,

the

53 — 66

HAMASAKI, D . , a n d E . MARG: E l e c t r o p h y s i o l o g i c a l s t u d y of

the posterior accessory optic tract. Am. J . Physiol. 199, 5 2 2 - 5 2 8 (1960b).

242

Mai,

J.

K.

D., and E . M A R G : Microelectrode study of accessory optic tract in the rabbit. Am. J . Physiol. 202, 480 to 486 (1962). H A N D A , Y . : On the relationship between optic tract and hypothalamus. Noshinkeiryoiki 9, 71 — 85 (1951). HANKE, V.: Das Gehirn eines bilateralen kongenitalen Anophthalmus. Arb. aus dem Neurologischen Institut an der Wiener Universität 10, 5 8 - 6 5 (1903). H A R T W I G , H . G.: Das visuelle System von Zonotrichia leucophryx gambelii. Neurohistologische Studien auf experimenteller Grundlage. Z. Zellforsch. 106, 556 — 583 (1970). H A R T W I G , H . G.: Electron microscopic evidence for a retinohypothalamic projection to the suprachiasmatic nucleus of Passer domesticus. Cell Tiss. Res. 153, 89 — 99 (1974). H A R T W I G , H.-G., and A . O K S C H E : Neurohistochemical and endocrine aspects of accessory optic pathways in two species. Gen. comp. Endoer. 18, 595 (1972). H A S S L E R , R . : Comparative anatomy of the central visual system in day- and night-active primates. In: Evolution of the Forebrain. Eds.: R. Hassler and H. Stephan. Georg Thieme Verlag, Stuttgart, Germany, 4 1 9 - 4 3 4 (1966). H A T S C H E K , R., und H . S C H L E S I N G E R : Der Hirnstamm des Delphins. Arb. aus d. Neurol. Inst, zu Wien, 9, 1 — 117 (1962). H A Y H O W , W. R . : An experimental study of the accessory optic fiber system in the cat. J . Comp. Neurol. 113, 281 to 314 (1959). H A Y H O W , W. R . : The accessory optic system in the marsupial phalanger Trichosurus vulpecula. An experimental degeneration study. J . Comp. Neurol. 126, 653 — 672 (1966). H A Y H O W , W . R., C. W E B B and A. J E R V I E : The accessory optic fiber system in the rat. J . Comp. Neurol. 115, 187 to 216 (1960). H A Y H O W , W. R., A. S E F T O N and C . W E B B : Primary optic centers of the rat in relation to the terminal distribution of the crossed and uncrossed optic nerve fibers. J . Comp. Neurol. 118, 2 9 5 - 3 2 2 (1962). HAMASAKI,

HAYMAKER, W . ,

E . ANDERSON

and

W . J . H . NAUTA:

The

hypothalamus. Ch. C. Thomas, Springfield 111. 1.969. H E D R E E N , J . C.: Diencephalic projection of the retina in the cat. Anat. Ree. 166, 317 (1970). H E I M E R , L . : Impairment of mating behavior in male following lesions in the preoptic-anterior hypothalamic continuum. Brain Res. 3, 2 4 8 - 2 6 3 (1967a). H E I M E R , L . : Silver impregnation of terminal degeneration. Brain Res. 5, 8 6 - 1 0 8 (1967b). H E I M E R , L . , and K . L A R S S O N : Impairment of mating behavior in male rat following lesions in the preopticanterior hypothalamic continuum. Brain Res. 3, 248—263 (1966/1967). HENDRICKSON, A . E . , M . E . WILSON a n d M . J . T O Y N E :

The

distribution of optic nerve fibers in Macaca mulatta. Brain Res. 23, 4 2 5 - 4 2 7 (1970). HENDRICKSON, A . E . ,

N.WAGONER

and

W . M. COWAN:

An autoradiographic and electron microscopic study of retino hypothalamic connections. Z. Zellforsch. 135, 1 - 2 6 (1972). HENLE, J.: Nervenlehre. In: Handbuch der Anatomie Vol. I I I , Vieweg, Braunschweig (1868). H E N S C H E N , S. E . : Über die hemianopische Pupillenreaktion. Klinische und anatomische Beiträge zur Pathologie des Gehirns. Neurol. Centralblatt 14, 5 1 1 - 5 1 2 (1895). H E N S C H E N , S. E . : Zentrale Sehstörungen. I n : M. Lewan-

dowsky's Handb. d. Neurologie, Vol. I, J . Springer, Berlin 891 (1910). H E R K E N H A M , M . , and W . J . H . N A U T A : Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber-of-passage problem. J . Comp. Neurol. 173, 1 2 3 - 1 4 6 . H E R R I C K , C. J . : The internal structure of the midbrain and thalamus of Necturus. J . Comp. Neurol. 28, 215 — 348 (1917). H E R R I C K , C. J . : The amphibian forebrain. I I I . The optic tracts and centers of Amblyostoma and the frog. J . Comp. Neurol. 39, 4 3 3 - 4 8 9 (1925). H E R R I C K , C. J . : The amphibian forebrain. V I . Necturus. J . Comp. Neurol. 58, 1 - 2 8 8 (1933). H E R R I C K , C. J . : The hypothalamus of Necturus. J . Comp. Neurol. 59, 3 7 5 - 4 2 9 (1934). H E R R I C K , C. J . : Cerebral fiber tracts of Amblystoma tigrinum in midlarval stages. J. Comp. Neurol. 71, 511 — 612 (1939). H E R R I C K , C. J . : Development of the optic nerves of Amblystoma. J . Comp. Neurol. 74, 4 7 3 - 5 3 4 (1941a). H E R R I C K , C. J . : The eyes and optic paths of the cutfish, Ameiurus. J . Comp. Neurol. 75, 2 5 5 - 2 8 6 (1941b). H E R R I C K , C. J . : Optic and postoptic systems of fibers in the brain of Necturus. J. Comp. Neurol. 75, 487 — 544 (1941c). H E R R I C K , C. J . : Optic and postoptic systems in the brain of Amblystoma tigrinum. J . Comp. Neurol. 77, 191 — 353 (1942). H E R R I C K , C. J . : The brain of the tiger salamander. University of Chicago Press. Chicogo 111. (1948). H E R Y , F., E. R O U E R and J . G L O W I N S K I : Daily variations of serotonin metabolism in the rat brain. Brain Res. 43, 4 4 5 - 4 6 5 (1972). H E R Z O G , F . : Über die Sehbahn des Ggl. opticum basale und die Fasersysteme am Boden des 3. Hirn-Ventrikels in einem Fall von Bulbusatrophie beider Augen. Deutsch. Ztschr. für Nervenheilk. 30, 223 — 238 (1906). HESS, A.: Optic centers and pathways after eye removal in fetal guinea pig. J . Comp. Neurol. 109, 91 — 115 (1958). H I C K E Y , T. L., and P. D. S P E A R : Retinogeniculate projections in hooded and albino rats: An autoradiographic study. Exp. Brain Res. 24, 5 2 3 - 5 2 9 (1976). H I L F E N H A U S , M . : Circadian rhythm of plasma renin activity, plasma aldosterone and plasma corticosterone in rats. Internat. J . Chronobiol. 3, 2 1 3 - 2 2 9 (1976). HILL, R . M., and E . MARG: Single cell responses of the nu-

cleus of the transpeduncular tract in rabbit to monochromatic light on the retina. J . Neurophysiol. 26, 249 — 257 (1963). H I N E S , M . : The brain of Ornithorhynchus anatinus. Phil, trans. Roy. Soc. (B) 217, 1 5 5 - 2 8 7 (1929). HIRSCHBERGER, W . : Vergleichend experimentell-histologische Untersuchungen zur retinalen Repräsentation in den primären visuellen Zentren einiger Vogelarten. Inaug.Diss. Frankfurt 1971. HISANO, N . ,

and J . retinal •(1972).

D . P . CARDINALI,

J . M.

ROSNER,

C. A . NAGLE

Pineal role in the duck extraphotoreeeption. Endocrinol. 91, 1318 — 1322

H . TRAMEZZANI:

and J . C. B O N B R I G H T , j r . : Intensity and pattern discrimination after lesions of the pretectal complex, accessory optic nucleus and ventral geniculate in pigeons. J . Comp. Neurol. 161, 1 - 1 8 (1975). H Ö K F E L T , T . : On the ultrastructural localization of noradHODOS, W . ,

Accessory Optic and Retino-Hypothalamic System renaline in the central nervous system of the rat. Z. Zellforsch. 79, 1 1 0 - 1 1 7 (1967). H Ö K F E L T , T.: Central monoaminergic systems and hypothalamic function. In: The hypothalamus. Eds.: L. Martini, M. Motta and F. Fraschini. Academic Press New York, 1 2 3 - 1 3 8 (1970). HÖKFELT, T.,

K. FUXE,

M . GOLDSTEIN,

O.

JOHANSSON,

H. F R A S E R and S . L . J E F F C O A T E : Immunofluorescence mapping of central monoamine and releasing hormone (LRH) systems. Anat. Neuroendocrinology, Int. Conf. Neurobiology of CNS-Hormone Interactions, Chapel Hill 1974, 3 8 1 - 3 9 2 (Karger, Basel 1975). H O F F M A N , G. E . : Immunogenicity of gonadotropin releasing factors in mammalian neurons. Anat. Ree. 187, 606 (1977). H O L B R O O K , J . R . , and H . S C H A P I R O : The accessory optic tract in the dog; a retino-entopeduncular pathway. J . Hirnforsch. 15, 3 6 5 - 3 7 6 (1974). H O L L W I C H , F . : Über die Bedeutung des „energetischen Anteils der Sehbahn" für die Regulation von Stoffwechselabläufen. Münch, med. Wschr. 94, 1 0 5 7 - 1 0 6 6 (1952). H O L L W I C H , F . : The influence of light via the eyes on animals alnd man. Ann. N.Y. Acad. Sei. 117, 1 0 5 - 1 2 8 (1964). H O L L W I C H , F., und B. D I E C K H U E S : Die Wirkung von Tagesund Kunstlicht auf den tierischen und menschlichen Organismus. Fortschr. Med. 90, 25 — 28 (1972). H O L M G R E N , N.: Zur Anatomie und Histologie des Vorderund Zwischenhirns der Knochenfische. Acta Zool. (Stockholm) 1, 1 3 7 - 3 1 5 (1920). H U B E R , G. C., and E. C. C R O S B Y : On thalamic and tectal nuclei and fiber paths in reptiles and mammals. J . Comp. Neurol. 40, 9 7 - 2 2 7 (1926). H U B E R , G. C., and E. C . C R O S B Y : The nuclei and fiber paths of the avian diencephalon with consideration of telencephalic and certain mesencephalic centres and connexions. J . Comp. Neurol. 48, 1 - 2 2 5 (1929). D. PARK,

H U B E R , G. C., E . C. CROSBY,

R . T . WOODBURNE,

L. A. GIL-

O. B R O W N and B . T A M T H A I : The mammalian midbrain and isthmus regions. J . Comp. Neurol. 78, 1 2 9 - 5 3 4 (1943). H U G H E S , A.: Topographical relationships between anatomy and physiology of the rabbit visual system. Docum. Ophthal. (Den Haag), 30, 3 3 - 1 6 0 (1971). H U M P H R E Y , T . : The telencephalon of the bat. J . Comp. Neurol. 65, 6 0 3 - 7 1 1 (1936). I B R A H I M , M., and W. M. S H A N K L I N : The diencephalon of the Coney, Hyrax syriaca. J . Comp. Neurol. 75, 427 to 485 (1941). I B U K A , N., and H. K A W A M U R A : Loss of circadian rhythm in sleep-wakefulness cycle in rat by suprachiasmatic nucleus lesions. Brain Res. 96, 76 — 81 (1975). I B U K A , N . , S . - I . T . I N O U Y E and H . K A W A M U R A : Analysis of sleep-wakefulness rhythms in male rats after suprachiasmatic nucleus lesions and ocular enucleation. Brain Res. 122, 3 3 - 4 7 (1977). I N G R A M , W. R . : The topography of the nuclei of the diencephalon of the cat. J . Comp. Neurol. 55, 333 — 394 (1932). LILAN,

J.

INGRAM, W . R . ,

F . L . HANNETT

and

S. W . RANSON:

The

topography of the nuclei of the diencephalon of the cat. J . Comp. Neurol. 55, 3 3 3 - 3 9 4 (1932). I N Z A N I , G . , e A. L E M O I G N E : Sulle origine e sull'andamento di varii fasci nervöse del cervello. (1861, quoted according to W. Krause, 1884.) Arch. Ital. de Biol. 12, 1 (1875). I T O , M., T. S H I I D A , N. Y A G I and M. Y A M A M O T O : Visual influence on rabbit horizontal vestibulo-ocular reflex presumably effected via the cerebellar flocculus. Brain Res. 65, 170 — 174 (1974).

243

and Y. M I J I S H I T A : The effects of chronic destruction of the inferior olive upon visual modification of the horizontal vestibulo-ocular reflex of rabbits. Proc. Jap. Acad. 51, 7 1 6 - 7 2 0 (1975). J A C O B O W I T Z , D. M.: Fluorescence microscopic mapping of CNS norepinephrine systems in the rat forebrain. Anat. Neuroendocrinology Int. Conf. Neurobiology of CNSHormone Interactions, Chapel Hill 1974, 368 — 380 (Karger, Basel 1975). J A C O B S , M . S., and P. J . M O R G A N E : Retino-hypothalamic connections in cetecea. Nature (Lond.) 203, 778 — 780 (1964). JAKWAY, J . S., and W. Riss: Retinal projections in the tiger salamander. Anat. Ree. 163, 203 (1969). J A K W A Y , J . S., and W. Riss: Retinal projections in the tiger salamander, Ambystoma tigrinum. Brain, Behav., Evol. 5, 4 0 1 - 4 4 1 (1972). J A N S E N , J . : A note in the optic tract in teleosts. Proc. kon. nederl. Akad. Wet. 32, 1 1 0 4 - 1 1 1 7 (1929). J E F F E R S O N , J . M.: A study of the subcortical connexions of the optic tract system of the ferret, with spec, reference to gonadal activation by retinal stimulation. J . Anat. (Lond.) 75, 1 0 6 - 1 3 4 (1940). J E L G E R S M A , G.: Die sensiblen und sensorischen Nervenbahnen und Centren. Neurol. Centralbl. 14, 290 — 300 (1895). J O H A N S S O N , N.-G.: Biosynthesis and secretion of hypothalamic hormones. In: E. S. E. Hafez and J . R. Reel (eds.) Ann Arbor Science Publ. Inc. Ann Arbor, Michigan 1976. ITO, M . ,

JURASKA, J . M., Ch. J . WILSON a n d P . M. GROVES: T h e

sub-

stantia nigra of the rat: A Golgi study. J . Comp. Neurol. 172, 5 8 5 - 6 0 0 (1977). K A C H I , T.: Circadian rhythm in number of granular vesicles in pinealocytes and the effect of lighting: Semiquantitative electron microscopic study. Anat. Ree. 187, 619 (1977). KAKOLEWSKI, J . W . ,

E . DEAUX,

J . CHRISTENSEN

and

B. CASE: Diurnal patterns in water and food intake and body weight changes in rats with hypothalamic lesion. Amer. J . Physiol. 221, 7 1 1 - 7 1 8 (1971). K A L R A , S. P.: Circadian rhythm in luteinizing hormonereleasing hormone (LH —RH) content of preoptic area during the rat estrous cycle. Brain Res. 104, 354 — 358 (1976). KANAGASUNTHERAM, R . ,

and

A . KRISHNAMURTI:

Eye

enu-

cleation and substantia nigra. Acta Anat. (Basel) 80, 4 6 0 - 4 6 4 (1971). K A R A M A N L I D I S , A. N., and J . M A G R A S : Retinal projections in domestic ungulates. I. The retinal projections in the sheep and pig. Brain Res. 44, 127 — 145 (1972). K A R A M A N L I D I S , A. N., and J . M A G R A S : Retinal projections in domestic ungulates. II. The retinal projections in the horse and the ox. Brain Res. 66, 2 0 9 - 2 2 5 (1974). K A R T E N , H. J . , and W. J . H. N A U T A : Organization of retinohypothalamic projections in the pigeon and owl, Anat. Ree. 160, 373 (1968). K A R T E N , H . J., and W. H O D O S : Telencephalic projections of the nucleus rotundus in the pigeon (Columba livia). J . Comp. Neurol. 140, 3 5 - 5 1 (1970). K E E F E R , D. A., and D. A. S T U M P F : Atlas of estrogen-concentrating cells in the central nervous system of the Squirrel monkey J . Comp. Neurol. 160, 4 1 9 - 4 4 2 (1975). K E L L Y , P. H., R. J . M I L L E R and J . L. N E U M E Y E R : Proceedings: Effect of aporphine alkaloids on central dopamine receptors. Br. J . Pharmacol. 54, 271 P (1975).

244

Mai,

J.

K.

Carboxylic esterases of the hypothalamus and neurohypophysis of the hedgehog. J . Roy. Micr. Soc. 83, 2 9 7 - 3 0 6 (1964). K I E R N A N , J . A.: On the probable absence of retino hypothalamic connections in five mammals and an amphibian. J . Comp. Neurol. 131, 4 0 5 - 4 0 8 (1967). K I Z E R , J . S.: Endocrine-induced alterations of monoamine metabolism in brain. Anat. Neuroendocrinology. Int. Conf. Neurobiology of CNS-Hormone Interactions, Chapel Hill, 1974, 4 0 1 - 4 0 8 (Karger, Basel, 1975). KIERNAN, J . A . :

K I Z E R , J . S.,

J . A . ZIVIN,

D . M . JACOBOWITZ

K I Z E R , J . S.,

M . PALKOVITS,

and

I. J .

Ko-

J . KEBABIAN

and

PIN : The nycthermal rhythm of plasma-prolactin: Effects of ganglionectomy, pinealectomy, constant light, constant darkness or 6-OH-dopamine administration. Endocrinology 96, 1 2 3 0 - 1 2 4 0 (1975). M . TAPPAZ,

Distribution of releasing factors, biogenic amines, and related enzymes in the bovine median eminence. Endocrinology 98, 685 — 695 (1976). K L E I N , D . C . , and J . L . W E L L E R : Indole metabolism in the pineal gland: A circadian rhythm in N-acetyltransferase. Science 169, 1 0 9 3 - 1 0 9 5 (1970). K L O S S O W S K I , B . : Über die intertractalen Fasern und die Leitungssysteme des Bodens des 3. Ventrikels. Arch. f. Psychiatr. 91, 3 7 - 7 4 (1930). K N A P P , H . , F . SCALIA and W . R i s s : The optic tracts of Rana pipiens. Acta neurol. Scand. 41, 325 — 355 (1965). K N A P P , H . , and D. S. K A N G : The visual pathways of the snapping turtle (Chelydra serpentina). Brain Behav. Evol. 1, 1 9 - 4 2 (1968). K N A P P , H . , and D . S. K A N G : The retinal projections of the side-necked turtle (Podocnemeis unifilis) with some notes on the possible origin of the pars dorsalis of the lateral geniculate body. Brain Behav. Evol. 1, 3 6 9 - 4 0 4 (1968). K N I G G E , K. M., D. SCHOCK and J . R. S L A D E K , jr.: Monoamines of median eminence. In: Brain Endocrine Interaction II. The Ventricular System. 2nd Int. Symp. Shizuoka 1974, 2 8 2 - 2 9 4 (Karger, Basel, 1975). K N O C H E , H.: Morphologisch experimentelle Untersuchungen über eine Faserverbindung der Retina mit den vegetativen Zentren des ZH und mit der Hypophyse. Z. Zellforsch. 45, 2 0 1 - 2 6 4 (1956). K N O C H E , H.: Die Verbindung der Retina mit den vegetativen Zentren des Zwischenhirnes und mit der Hypophyse. Verh. Anat. Ges. 53, 1 4 0 - 1 4 8 (1957). K N O C H E , H.: Die retino-hypothalamische Bahn von Mensch, Hund und Kaninchen. Z. mikr.-anat. Forsch. 63, 461 bis 486 (1957). K N O C H E , H.: Über die Ausbreitung und Herkunft der nervösen Nodulusfasern in Hypothalamus und Retina. Z. Zellforsch. 48, 6 0 2 - 6 1 6 (1958). K N O C H E , H.: Ursprung, Verlauf und Endigung der retinohypothalamischen Bahn. Z. Zellforsch. 51, 658 — 704 (1960). K N O L L : Beiträge zur Anatomie und Physiologie. C . Eckhardt, Vol. 4 (1869) (cited according to N. Tümianzew, 1898). K N O O K , H . L . : The fibre-connections of the forebrain series: Studies in Neuro-Anatomy, J . Droogleever Fortuyn and W. J . C. Verhart (Eds.), Van Gorcum & Comp. N. V., Assen, 1965 K Ö L L I K E R , A. v.: Handbuch der Gewebelehre. W. Engelmann, Leipzig (1889 — 1902). K O P P E N , M.: Beiträge zur vergleichenden Anatomie des Centrainervensystems der Wirbeltiere. Morphologische Arbeiten, G. Schwalbe (Ed.) Vol. I, 1 3 2 - 1 5 1 (1892). K O I K E G A M I , H.: Beiträge zur Kenntnis der Kerne des HypoM. J . BROWNSTEIN:

thalamus bei Säugetieren. Arch. f. Psychiatr. 107, 742 bis 774 (1938). K O N O P K A , R. J., and S. B E N Z E R : Clock mutants of Drosophila melanogaster. Proc. Nat. Acad. Sei., N.Y. 68, 2 1 1 2 - 2 1 1 6 (1971). K O S A K A , K . , und K . H I R A I W A : Zur Anatomie der Sehnervenbahnen und ihrer Zentren. Folia Neurobiol. (Lpz.) 9, 3 6 7 - 3 8 9 (1915). K O S A R E V A , A. A. : Projection of optic fibres to visual centers in a turtle (Emys orbicularis). J. Comp. Neurol. 130, 2 6 3 - 2 7 6 (1967). KOSTOVIC, I. : The terminal distribution of accessory optic fibers in the rat. Brain Res. 31, 2 0 2 - 2 0 6 (1971). K R A U S E , W. : Anatomie des Kaninchens. Verlag W. Engelmann, Leipzig, Und ed. 1884. K R A Y N I A K , P. F. : Projections of the septum in the pigeon, Columba livia. Anat. Ree. 187, 630 (1977). K R E H T , H. : Über die Faserzüge im Zentralnervensystem von Salamandra maculosa L. Zeits. mikr.-anat. Forschg. 23, 2 3 9 - 3 2 0 (1930). K R E H T , H. : Über die Faserzüge im Zentralnervensystem von Proteus anguineus Laur. Zeits. mikr.-anat. Forsc'hg. 25, 3 7 6 - 4 2 7 (1931). KRIEG, W. J . S. : The hypothalamus of the albino rat. J . Comp. Neurol. 55, 1 9 - 8 9 (1932). K U C H A R C Z Y K , J., and G. J . M O G E N S O N : The role of mesencephalic structures in thirst induced by centrally administered angiotensin II. Brain Res. 126, 2 2 5 - 2 4 1 (1977). K U D O , K . : Contributions to the knowledge of the brain of bony fishes. Proc. Kon. Acad. v. Wetensch. Amsterdam 26, 6 5 - 7 8 (1923). L A A T S C H , R. H . : The retinal projection in the accessory optic tract of the guinea pig. Anat. Ree. 163, 214 (1969). LADD, E. D.: Retinofugal projections of the Mongolian gerbil, Meriones unguiculatus. Anat. Ree. 187, 632 (1977). L A E M L E , L . K. : Retinal projections of Tupaia, Nycticebus, Galago, and Saimiri. Anat. Ree. 157, 273 — 274 (1967). L A E M L E , L . K. : Retinal projections of Tupaia glis. Brain Behav. Evol. 1, 4 7 3 - 4 9 9 (1968). L A E M L E , L . K., and C. R. N O B A C K : The visual pathways of the lorisid lemurs. J . Comp. Neurol. 138, 49 — 62 (1970). L A R U E L L E , L. : Le système végétatif méso-diencéphalique, partie anatomique. Rev. neurol. 1 (61), 809 — 842 (1934). L A S H L E Y , K. S. : The mechanism of vision. II. The influence of cerebral lesions upon the threshold of discrimination for brightness. J . genet. Psychol. 37, 461 — 480 (1930). L A S H L E Y , K. S.: The mechanism of vision. VII. The projection of the retina upon the primary optic centers of the rat. J. Comp. Neurol. 59, 3 4 1 - 3 7 3 (1934). L A T I E S , A. M., and J . M. S P R A G U E : The projection of optic fibers to the visual centers in the cat. J . Comp. Neurol. 127, 3 5 - 7 0 (1966). L A W S O N , D. M., and R. R. G A L A : The interaction of dopaminergic and serotonergic drugs on plasma prolactin in ovariectomized, estrogen-treated rats. Endocrinology 98, 4 2 - 4 7 (1976). L Â Z Â R , G.: The projection of the retinal quadrants on the optic centres in the frog. A terminal degeneration study. Acta Morphol. Acad. Sei. Hung. 19, 3 2 5 - 3 3 4 (1971). L Â Z Â R , G. : Role of the accessory optic system in the optokinetic nystagmus of the frog. Brain Behav. Evol. 5, 4 4 3 - 4 6 0 (1973). L Â Z Â R , G. : Transneuronal transport in the frog visual system. Brain Res. 109, 6 2 3 - 6 2 7 (1976). L Â Z Â R , G., and G. S Z É K E L Y : Distribution of optic terminals

Accessory Optic and Retino-Hypothalamic System in the different optic centres of the frog. Brain Res. 16, 1 - 1 4 (1969). L E ' B E U X , Y. J . : An ultrastructural study of the neurosecretory cells of the medial vascular prechiasmatic gland, the preoptic recess and the ant. part of the suprachiasmatic area. I. Cytoplasmic inclusions resembling nucleoli. Z. Zellforsch, mikroskop. Anat. 114, 4 0 4 - 4 4 0 (1971). L E F R A N C , G . : Recherches morphologiques et expérimentales sur les relations hypothalamo-préhypophysaires. Thesis, Alger (1961) (cited in: A. Hendrickson et al., 1972). L E F R A N C , G., et J . B A R R Y : Etudes des voies optiques accessoires chez le cobaye. C. R. Soc. Biol. (Paris) 155, 7 4 6 - 7 4 7 (1961). L E G R O S C L A R K , W. E. : The thalamus of Tupaia minor. J . Anat. (Lond.) 63, 1 1 7 - 2 0 6 (1929). L E G R O S C L A R K , W . E . : The thalamus of Tarsius. J . Anat. (Lond.) 64, 3 7 1 - 4 1 4 (1930). L E G R O S C L A R K , W . E . : Degeneration of the optic tract fibers in the rat. J . Anat. (Lond.) 66, 138 (1931). L E G R O S C L A R K , W . E . : An experimental study of thalamic connections in the rat. Phil. Trans. Roy. Soc. Lond. (Ser. B) 222, 1 - 2 8 (1932). L E G R O S C L A R K , W . E . : The medial geniculate body and the nucleus isthmi. J . Anat. (Lond.) 67, 536 — 548 (1933a). L E G R O S C L A R K , W . E . : The brain of Insectívora. Proc. Zool. Soc. (Lond.) J a n . 9 7 5 - 1 0 1 3 (1933b). L E G R O S C L A R K , W . E. : The Hypothalamus. Morphological, functional, clinical and surgical aspects. Edinburgh, Oliver and Boyd 1938. L E G R O S C L A R K , W . E . : The visual centres of the brain and their connexions. Phys. Rev. 22, 205 — 232 (1942). L E GROS CLARK, W . E.,

T. MC KEOWN

and

S.

ZUCKERMAN:

Visual pathways concerned in gonadal stimulation in ferrets. Proc. Roy. Soc. (Lond.) B 126, 4 4 9 - 4 6 8 (1939). L E N H O S S É K , M. v. : Beobachtungen am Gehirn des Menschen. Anat. Anzeiger 2, 450 — 461 (1887). L E N N , N . J . : An electron microscopic study of accessory optic endings in the rat medial terminal nucleus. Brain Res. 43. 6 2 2 - 6 2 8 (1972). L E N N , N. J., B. B E E B E and R. Y. M O O R E : Postnatal development of the suprachiasmatic hypothalamic nucleus of the rat. Cell Tiss. Res. 178, 4 6 3 - 4 7 5 (1977). LENT, R.,

L . A . CAVALCANTE

and

C. E .

ROCHA-MIRANDA:

Retinofugal projections in the opossum, an anterograde degeneration and radioautographic study. Brain Res. 107, 9 - 2 6 (1976). L E O N O W A , O . v. : Beiträge zur Kenntnis der sekundären Veränderungen der primären optischen Zentren und Bahnen in Fällen von kongenitaler Anophthalmie und Bulbusatrophie bei neugeborenen Kindern. Arch. f. Psych, u. Nervenheilk. 28, 5 1 - 9 6 (1895). L E O N A R D E L L I , J . , J . B A R R Y et M. P. D U B O I S : Mise en évidence par immunofluorescence d'un constituant immunologiquement apparenté au L H — R F dans l'hypothalamus et l'eminence mediane chez les mammifères. C.R. Acad. Sei. (D) (Paris) 276, 2 0 4 3 - 2 0 4 6 (1973). L E V I - M O N T A L C I N I , R . : N G F : An uncharted route. In: The Neurosciences : Paths of discovery. Eds. : F. G. Worden, J . P. Swazey and G. Adelman. The MIT Press, Cambridge, Mass. 2 4 5 - 2 6 5 (1975). L E V I N S O H N , G. : Experimentelle Untersuchungen über die Beziehungen des vorderen Vierhügels zum Lichtreflex. Graefes Arch. (1909) (quoted according to R. A. Pfeifer, 1930). LIN, H. : On the probable absence of connections between the retina and the hypothalamus in the cat. Anat. Ree. 172, 356 (1972).

245

LIN, H . : Letter: Retinohypothalamus connections. Invest. Ophthalmol. 12, 7 1 4 - 7 1 5 (1973). L I N , H . , and W. R. I N G R A M : Probable absence of connections between the retina and the hypothalamus in the cat. Exp. Neurol. 37, 2 3 - 3 6 (1972a). L I N , H., and W. R. I N G R A M : An anterior component of the accessory optic system of the cat, with evidence for the absence of reticuloretinal fibres. E x p . Neur. 37, 37 — 49 (1972b). L I N , H., M. A L E X A N D E R and R. A. G I O L L I : The accessory optic fibre system of the golden hamster with special reference to retinohypothalamic projection. Anat. Ree. 186, 4 5 1 - 4 6 0 (1976). L I N A U T S , M.: The organization of midbrain and thalamic projections to the inferior olive: a study using the autoradiographic technique. Anat. Ree. 187, 638 (1977). L I S K , R. D., and L. R. K A N N W I S C H E R : Light: Evidence for its direct effect on hypothalamic neurons. Science, 146, 2 7 2 - 2 7 3 (1964). LISK, R. D.: Sexual behavior: Hormonal control. In: Neüroendocrinology. E d s . : L. Martini and W. F. Ganong. Vol. 2, 197 — 239, Academic Press, New York, London (1967). L I T T E R I A , M.: Inhibitory action of neonatal estrogenization on the incorporation of 3 H lysine into proteins of specific limbic and paralimbic neurons of the adult rat. Brain Res. 127, 1 6 4 - 1 6 7 (1977). LOEPP, W. H . : Über die zentralen Opticusendigungen beim Kaninchen. Anat. Anz. 40, 309 (1912). L Ö W E , L . : Beiträge zur Anatomie und zur Entwicklungsgeschichte des Nervensystems der Säugetiere und des Menschen. Vol. 1. Die Morphogenesis des centralen Nervensystems. Denicke's Verlag Berlin 1880. Loo, Y. T . : The forebrain of the opossum, Didelphys virginiana. Part II. Histology. J . Comp. Neurol. 52,1 — 148 (1931). LUND, R. D.: Uncrossed visual pathways of hooded and albino rats. Science 149, 1 5 0 6 - 1 5 0 7 (1965). L U N D , R. D., and J . S. L U N D : The visual system in the mole, Talpa europaea. E x p . Neurol. 13, 302 — 316 (1965). M A E K A W A , K., and J . I. S I M P S O N : Climbing fiber activation of Purkinje cells in the flocculus by impulses transferred through the visual pathway. Brain Res. 39, 245 to 251 (1972). M A E K A W A , K., and J . I. S I M P S O N : Climbing fiber responses evoked in the vestibulocerebellum of rabbit from visual system. J . Neurophysiol. 36, 6 4 9 - 6 6 6 (1973). M A G N U S , H . : Die Entstehung der reflektorischen Pupillenbewegung. Klin. Monatsbl. f. Augenheilk. 1888. (according to S. Bernheimer 1899). MAI, J . K . : Paper presented at the 71st Congress of the Verh. Anat. Ges. 71, 1 7 7 - 1 8 1 (1977) Anatomical Society, Warnemünde (GDR) 1976. MAI, J . K . : Quantitative autoradiographische Untersuchungen am subcorticalen optischen System der Albinoratte. Dissertation Düsseldorf 1 — 281 (1976). M A I , J . K., and E. J U N G E R : Quantitative autoradiographic light- and electron microscopic studies on the retino hypothalamic connections in the rat. Cell. Tiss. Res. 183, 221 to 237 (1977) MAI, J . K . : Veränderte Verlaufs- und Einigungsweise optischer Fasern im Hypothalamus nach einseitiger Enucleation. Paper presented at the Fourth European Anatomical Congress, Basel (1977). M A K A R A , G. B., M . C . H A R R I S and K. M . S P Y E R : Identification and distribution of tubero infundibular neurones. Brain Res. 40, 2 8 3 - 2 9 0 (1972).

246

Mai,

J.

K.

MAKARA, G. B., and L. HODÂCS: Rostral projections from the hypothalamic arcuate nucleus. Brain Res. 84, 23 — 29 (1975). MALONE, E . F . : The nuclei tuberis and the so-called ganglion opticum basale. John Hopkins Hosp. Rep., Monographs N.S. 6 (1914). MANGILI, G . , M . MOTTA a n d L . MARTINI: C o n t r o l of

adreno-

corticotropic hormone secretion. In : Neuroendocrinology. E d s . : L. Martini and W. F . Ganong V o l . 1 , 2 9 7 - 3 7 0 , Academic Press, New York, London (1966). MARBURG, O. : Basale Opticuswurzel und tr. peduncularis transversus. Zbl. Physiol. 17, 3 0 - 3 1 (1903). MARBURG, O. : Mikroskopisch-topographischer Atlas des menschlichen Zentralnervensystems. Franz Deuticke, Leipzig and Wien 1910. MARBURG, O. : Primary endings of the optic nerve in man and animals. Ach. Ophthal. 28, 61 — 78 (1942). MARCHI, V., e G. ALGERI: Sulle degenerazioni discendenti consecutive a lesioni sperimentale in diverse zone della corteccia cerebrale. Riv. sper. di Freniat. 11, 492 — 494 (1885). MARG, E . : The accessory optic system. Ann. N . Y . Acad. Sci. 117, 3 5 - 5 . 1 (1964). MARG, E . : Neurophysiology of the accessory optic system. I n : Handbook of Sensory Physiology. Vol. V I I / 1 3 Ed. R . J u n g Springer Verlag, Heidelberg, N . Y . 1 0 3 - 1 1 1 (1973). MARG, E . ,

D . HAMASAKI

and

R . GIOLLI:

Responses

of

the

posterior accessory optic tract to photic stimulation of the retina and electrical stimulation of the optic nerve in rabbit. X X I . Internat. Congr. Physiol. Sciences 176 (1959). MARIE, P., et A. LÉRI: Persistance d'un faisceau intact dans les bandelettes optiques après atrophie complète des nerfs: le "faisceau résiduaire de la bandelette". Le ganglion optique basai et ses connexions. Revue neurologique 13, 4 9 3 - 5 0 3 (1905). MARTINI, L. : Recent advances in the study of the hypothalamic releasing factors. I n : Neurosecretion — The Final Neuroendocrine Pathway. Eds. : F . Knowles and L. Vollrath. 1 3 5 - 1 4 7 , Springer Verlag Berlin, Heidelberg, New Y o r k 1974. MARTINI, L . ,

F . FRASCHINI

and

M. MOTTA:

Neural

control

of anterior pituitary functions. Recent Prog. Horm. Res. 24, 4 3 9 - 4 8 5 (1968). MASON, C. A . ,

and

D . W . LINCOLN:

Visualization

of

the

retino-hypothalamic projection by cobalt precipitation. Cell Tiss. Res. 168, 1 1 7 - 1 3 1 (1976). MASSAUT, H. : Experimentaluntersuchungen über den Verlauf der den Pupillarreflex vermittelnden Fasern. Arch. f. Psychiat. 28, 4 3 2 - 4 5 6 (1896). MASSOPUST, L . C., jr., a n d H . G . D A I G L E : H y p o t h a l a m i c a n d

anteroventral mesencephalic photic responses in the cat. E x p . Neurol. 3, 4 7 6 - 4 8 6 (1961). MAYERSBACH, H. V. : The cellular aspects of biorhythms. Ed. H. von Mayersbach Springer Verlag Berlin, Heidelberg, New Y o r k 1967. MCCANN, S . M . ,

A. P . S. DHARIWAL

and

J . C. P A T E :

Regu-

lation of the adenohypophysis. Ann. Rev. Physiol. 30, 5 8 9 - 6 4 0 (1968). MCCANN, S . M . , L . KRULICH, M . QUIJADA, J . WHEATON

and

R . L. Moss : Gonadotropin-releasing factors. Sites of production, secretion and action in the brain. I n : Anatomical Neuroendocrinology Eds. W. Stumpf and L. Grant 185 — 191, Karger, Basel 1975. MEADER, R . G. : The optic system of a teleost, Holocentrus.

I. The primary optic pathways and the corpus geniculatum complex. J . Comp. Neurol. 60, 361 — 407 (1934). MEIER, R . E . : Retinohypothalamic pathway in the avian brain. Experientia 29, 746 (1973). MEIER, R . E . : Autoradiographic evidence for a direct retinohypothalamic projection in the avian brain. Brain Res. 53, 4 1 7 - 4 2 1 (1973). MEIKLE, T . H . , j r . , a n d J . M. SPRAGUE: T h e n e u r a l o r g a n i -

zation of the visual pathways in the cat. Int. Rev. Neurobiol. 6, 1 4 9 - 1 8 9 (1964). MENDEL, E . : Über reflectorische Pupillenstarre. Dtsch. Med. Wochenschr. 15, 9 5 7 - 9 5 8 (1889). MERGNER, H . : Untersuchungen am Organon vasculosum laminae terminalis (Crista supraoptica) im Gehirn einiger Nagetiere. Zool. J b . Abt. Anat. u. Ontog. 77, 289 — 356 (1959). MESDAG, T. M.: Bijdrage tot de ontwikkelingsgeschiednis van de struktuur der hersenen bij het Kipembryo. Dissertation, Groningen 1909. MESS, B.,

F . FRASCHINI,

M . MOTTA

and

L.MARTINI:

The

topography of the neurones systhesizing the hypothalamic releasing factor. I n : Proc. 2nd Int. Congr. Hormonal Steroids. E d s . : L. Martini, F. Fraschini and M. Motta. No. 132, 1004 — 1013, Excerpta Medica, Amsterdam, 1966. M E Y E R , D . C., a n d W . B . QUAY: H y p o t h a l a m i c a n d s u p r a -

chiasmatic uptake of serotonin in vitro: Twenty-fourhour changes in male- and proestrous female rats. Endocrinology 98, 1 1 6 0 - 1 1 6 5 (1976). MEYNERT,

T.:

1870

(Cited

according

to

A.

KÖLLIKER,

1896). MEYNERT, T . : Vom Gehirn der Säugetiere. I n : Strieker's Handbuch der Lehre von den Geweben der Menschen und der Tiere. Vol. I I , W . Engelmann, Leipzig, 694 — 808 (1872). MILLS, J . N.,

D.S.MINORS

and

J . M. WATERHOUSE :

The

circadian rhythms of human subjects without timepieces or indication of the alteration of day and night. J . Physiol. (Lond.) 240, (3), 5 6 7 - 5 9 4 (1974). MINKOWSKI, M.: Experimentelle Untersuchungen über die Beziehungen der Großhirnrinde und der Netzhaut zu den primären optischen Zentren, besonders zum corpus geniculatum externum. Arb. Hirnanat. Inst. Zürich 7, 2 5 8 - 3 6 2 (1914). MINKOWSKI, M.: Über den Verlauf, die Endigung und die zentrale Repräsentation von gekreuzten und ungekreuzten Sehnervenfasern bei einigen Säugetieren und beim Menschen. Schweiz. Arch. Neurol. Psychiat. a) 6, 201 — 252 (1920), b) 7, 2 6 8 - 3 0 3 (1920). MIRTO, D . : Sulla fina anatomia della regioni peduneulare e subthalamica nell' uomo. Nota preliminare. Rev. di patol. nervosa e mentale, Vol. I (1896) (cited according to Ramon Y Cajal, p. 717, 1904). MONAKOW, C. v.: Über einige durch Exstirpation circumscripter Hirnrindenregionen bedingte Entwicklungshemmungen des Kaninchenhirns. Arch. Psychiat. Nervenkrh. 12, 1 4 1 - 1 5 6 und 5 3 5 - 5 4 9 (1882). MONAKOW, C. V. : Experimentelle und pathologisch-anatomische Untersuchungen über die Beziehungen der sogenannten Sehsphäre zu den infracorticalen Opticuszentren und zum N. opticus. Arch. f. Psychiatr. 14, 699 bis 751 (1883). MONAKOW, C. v . : Experimentelle und pathologisch-anatomische Beiträge zur Kenntnis der optischen Leitungsbahnen und Zentren. Korrespondenzblatt für Schweiz. Ärzte 18 (in: C. U. Ariens Kappers et al. 1960). MONAKOW, C. v . : Experimentelle und pathologisch-anato-

Accessory Optic and Retino-Hypothalamic System mische Untersuchungen über die optischen Centren und Bahnen. Arch. f. Psychiatr. 20, 7 1 4 - 7 8 4 (1889). MONAKOW, C. V. : Gehirnpathologie. 2. Aufl. A. Holder, Wien 1905. MOELI, C.: Über die Pupillenstarre bei der progressiven Paralyse. Archiv f. Psychiat. 18, 1 - 3 3 (1887). MOELI, C.: Veränderungen des Tractus und Nervus opticus bei Erkrankungen des Occipitalhirns. Arch. f. Psychiat. 22, 7 3 - 1 2 0 (1889). MOELI, C.: Über das zentrale Höhlengrau bei vollständiger Atrophie des Sehnerven. Arch. f. Psychiat. 39 (1905). MÖLLENDORF, W . v.,

und

W . BARGMANN:

Handbuch

der

mikroskopischen Anatomie des Menschen. Vol. I I I : Haut und Sinnesorgane, part I V 158 — 163, Springer Verlag, Berlin, Göttingen, Heidelberg, New York 1964. MOORE, R . Y . : Pineal response to light: Mediation by the accessory optic system in the monkey. Nature (Lond.) 222, 7 8 1 - 7 8 2 (1969). MOORE, R. Y . : Visual pathways controlling neuroendocrine function. I n : Progress Endocrinol. Excerpta Medica Foundation Amsterdam 184, 4 9 0 - 4 9 4 (1969). MOORE, R . Y . : Retino-hypothalamic projection in mammals. A comparative study. Brain Res. 49, 4 0 3 - 4 0 9 (1973). MOORE, R . Y . : Central regeneration and recovery of function: The problem of collateral reinnervation. In: Plasticity and Recovery of Function in the Central Nervous System. Eds.: D. G. Stein, J . J . R o s e n and N. Butters. Academic Press, New York 111 — 128 (1974). MOORE, R . Y . ,

A. HELLER,

R . J . WURTMAN

and

J.

AXEL-

ROD : Visual pathway mediating pineal response to environmental light. Science 155, 220 — 223 (1967). MOORE, R . Y . ,

A. HELLER,

R . K . BHATNAGER,

R. J.

WURT-

MAN and J . AXELROD: Central control of the pineal gland: Visual pathways. Arch. Neurol. 18, 208 — 218 (1968). MOORE, R . Y . ,

F . KARAPAS a n d N. J . L E N N : A

retinohypo-

thalamic projection in the rat. Anat. Ree. 169, 382 — 383 (1971). MOORE, R . Y . , a n d N . J . L E N N : A r e t i n o - h y p o t h a l a m i c

pro-

jection in the rat. J . Comp. Neurol. 146, 1 — 14 (1972). M O O R E , R . Y . , a n d V . B . E I C H L E R : LOSS o f c i r c a d i a n

adrenal

corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res. 42, 2 0 1 - 2 0 6 (1972). MOORE, R . Y . , a n d D . C. K L E I N : V i s u a l p a t h w a y s a n d t h e

central neural control of a circadian rhythm in pineal serotonin N-acetyl-transferase activity. Brain Res. 71, 1 7 - 3 3 (1974). MOORE, R . Y., and V. B . EICHLER: Central neural mechanisms in diurnal rhythm regulation and neuroendocrine responses to light. Psychoneuroendocrinology 1, 265 — 279 (1976). MORISHITA, H . ,

M . KAWAMOTO,

S. KUROIWA,

M . TOMIOKA,

N . NAGAMACHI,

H . MITANI,

K.

HIGUCHI,

T . OZASA

and

H. ADACHI: Developmental changes in the hypothalamic nuclei in perinatal, neonatal and infant rats. Brain Res. 104, 3 5 9 - 3 6 2 (1976). MOSINGER, M.: Anatomie de L'hypothalamus et du sousthalamus e'largi. Schweiz. Arch. f. Neur. 65, 135 — 186 (1950). MOSINGER, M.: Neuro-endocrinologie et neuro-ergonologie: leur role an pathologie. Masson, Paris 1954. MOSZKOWSKA, A . ,

A. KORDON

and

I. E B E L S :

Biochemical

fractions and mechanisms involved in the pineal modulation of pituitary gonadotropin release. I n : The pineal gland. (Eds.): G. E . W. Wolstenholme and J . Knight. A Ciba Foundation Symposium, Churchill Livingston, London, 2 4 1 - 2 5 5 (1971).

MÜNZER, E . , u n d H . W I E N E R :

Das Zwischen- und

247

Mittel-

hirn des Kaninchens und die Beziehungen dieser Teile zum übrigen Centrainervensystem, mit besonderer Berücksichtigung der Pyramidenbahn und Schleife. Monatsschr. Psychiat. Neurol. 12, 2 4 1 - 2 7 9 (1902). NAGLE, C. A.,

D . P . CARDINALI

and

J . M. ROSNER:

Light

regulation of rat retinal hydroxyindole-O-methyl-transferase (HIOMT) activity. Endocrinology 91, 423 — 426 (1972). NAKAMURA, S., and J . TIGGES: Lipid droplets in the lateral terminal nucleus of the accessory optic system in galago (primates) Z. Zellforsch, mikroskop. Anat. 106, 550 — 555 (1970). NANCE, D. M.: Effects of small hypothalamic and preoptic lesions on gonadotropin control and reproductive behavior in rat. Anat. Ree. 187, 664 (1977). NAUTA, W. J . H . : Über die sog. terminale Degeneration im ZNS und ihre Darstellung durch Silberimprägnation. Habilitationsschrift, Zürich 1951. NAUTA, W . J . H . ,

and

J . J . VAN S T R A A T E N :

The

primary

optic centers of the rat. An experimental study by the "bouton" method. J . Anat. (Lond.) 81, 127 — 134 (1947). NAUTA, W . J . H . , a n d W . H A Y M A K E R :

Retino-hypothalamic

connections. I n : The Hypothalamus. Ed. W. Haymaker, E . Anderson and W. J . H. Nauta, C. Th. Springfield, 111. 1 8 7 - 1 8 9 (1969). NEARY, T. J . : An autoradiographic study of the retinal projections in some members of "archaic" and advanced anuran families. Anat. Res. 184, 487 (1976). NICHTERLEIN, O. E . ,

and

T. GOLDBY:

An

experimental

study of optic connections in the sheep. J . Anat. (Lond.) 78, 5 9 - 6 7 (1944). NIIMI, K . ,

T . TAKIMOTO,

S. KISHI

and

M. KOIZUKA:

The

terminations of optic fibers in the rabbit as studied by the Nauta method. Acta Anat. Japon. 36, 333 (1961). NISHINO, H . , a n d K . KOIZUMI: R h y t h m i c a c t i v i t y of n e u -

rons in the lateral hypothalamic area and ventromedial nuclei. Fed. Proc. 34, 424 (1975). NISHINO, H . ,

K . KOIZUMI a n d

C. M c C . B R O O K S :

Control

of

the suprachiasmatic nuclei of hypothalamus. Physiologist 18, 335 (1975). NISHINO, H . ,

K . KOIZUMI a n d C. M c C B R O O K S :

T h e role

of

suprachiasmatic nuclei of the hypothalamus in the production öf circadian rhythm. Brain Res. 112, 45 — 59 (1976). NISHINO, H . ,

and

K . KOIZUMI:

Responses

of

neurons

in

the suprachismatic nuclei of the hypothalamus to putative transmitters. Brain Res. 120, 1 6 7 - 1 7 2 (1977). NOLL, A.: Zur Kenntnis des Verlaufes der Pupillenfasern beim Vogel. Pflügers Arch. 196, 6 2 9 - 6 3 6 (1922). NORTHCUTT, R . G.: Retinofugal pathways in fetal dogfish pups, Squalus acanthias: An autoradiographic study. Anat. Ree. 184, 4 8 9 - 4 9 0 (1976). NORTHCUTT, R . G., a n d A . B . B U T L E R : R e t i n a l

projections

in the Northern water snake Natrix sipedon sipedon. J . Morph. 142, 1 1 7 - 1 3 6 (1974). NORTHCUTT, R . G . ,

and

A. B . BUTLER:

Retinofugal

path-

ways in the lingnose gar, Lepisosteus osseus (Linnaeus). J . Comp. Neurol. 166, 1 - 1 5 (1976). NOVOKHATSKII, A . S.,

and

L . L . GIRSHMAN :

Anatomical

connections of the optic tracts with the hypothalamic region. Vopr. Neirooftalm. 58, 7 — 38 (1958) from: Exc. Med. I : Anat. Anthropol. Embryol.Histol. 14, 563 (1960). OBERSTEINER, H.: Anleitung beim Studium des Baues der

248

Mai,

K.

J.

nervösen Centraiorgane im gesunden und kranken Zustande. F. Deuticke Leipzig, Wien Ist ed. 1888, Und ed. 1892, 5th ed. 1912. O B E R S T E I N E R , H.: Handbuch der Lehre vom Bau des Centralen Nervensystems, p. 390 (1896). (Cited according to N. Tümianzew, 1898.) O K S C H E , A.: Optico-vegetative regulatory mechanisms of the diencephalon. Anat. Anz. 108, 320 — 329 (1960). O K S C H E , A.: Retino-hypothalamic pathways in mammals and birds. In: La photorégulation de la reproduction chez les oiseaux et les mammiféres. Eds. J . Benoit et J . Assenmacher, 151 — 165, Centre national de la Recherche scientifique, Paris 1970. O K S C H E , A., and D . S . F A R N E R : Neurohistological studies of the hypothalamo-hypophysial system of Zonotrichia leucophrys gambelii with special attention to its role in the control of reproduction. Erg. Anat. Entwicklungsgesch. 48 (4), 1 - 1 3 6 (1974). OKSCHE, A., H . KIRSCHSTEIN, H . - G . HARTWIG, H . J .

OEHM-

and D. S. F A R N E R : Secretory parvocellular neurons in the rostral hypothalamus and the tuberal complex of passer domesticus. Cell Tiss. Res. 149, 363 — 370 (1974). O K S C H E , A., and H.-G. H A R T W I G : Photoneuroendocrine systems and the third ventricle. In: Brain-endocrine interaction. I I . The ventricular system in neuroendocrine mechanisms. 2nd. Int. Symp., Shizuoka, 1974. Eds.: K. M. Knigge, D. E. Scott, H. Kobayashi and S. Ishii. 4 0 - 5 3 Karger, Basel 1975. O S B O R N , H. F . : A contribution to the internal structure of the Amphibian brain. Journ. Morph. 2, 51 — 96 (1888). O ' S T E E N , W . K . , and G . M . V A U G H A N : Radioactivity in the optic pathway and hypothalamus of the rat after intraocular injection of tritiated 5-hydroxytrytophan. Brain Res. 8, 2 0 9 - 2 1 2 (1968). O V E R B O S C H , J . F. A.: Experimenteel-anatomische onderzoekingen over de projectie der retina in het centrale zenuwstesel. Academisch Proefschrift, Amsterdam 1927. P A C K E R , A. D.: An experimental investigation of the visual system in the phalanger, Trichosurus vulpécula. J . Anat. 75, 3 0 9 - 3 2 9 (1941). KE

PACKMAN,

P.

M.,

R.

L.

BOSHANS

and

M.

J.

BRAGDON:

Quantitative histochemical studies of the hypothalamus. Dehydrogenase enzymes during the estrons cycle. Neuroendocrinology 22, 117 — 126 (1976). P A L M G R E N , A.: Embryological and morphological studies in the midbrain and cerebellum of Vertebrates. Acta Zool. 2 , 1 - 9 4 (1921). PAPEZ, J . W . : Comparative Neurology. Thomas Crowell Company, N.Y. 1929; Reprint: Hafner Publ. Co. N.Y. 1961. P A P E Z , J . W . , and L . R . A R O N S O N : Thalamic nuclei of pithecus (macacus) rhesus I. Ventral thalamus II. Dorsal thalamus. Archives Neur. Psych. 32, 1 — 26 (1934). P A S I K , P . , and T. P A S I K : A comparison between two types of visually-evoked nystagmus in the monkey. Acta Otolaryngol. (Suppl.) (Stockholm) 3 0 - 3 7 (1975).

PASIK, T.,

P . PASIK,

J . HÁMORI

and

J.

SZENTÁGOTHAI:

Nucleus of the accessory optic tract: Electron microscopic analysis in normal and eye-enucleated monkeys. Trans. Am. Neurol. Assoc. 95, 3 0 2 - 3 0 5 (1970). P A S I K , T., and P . P A S I K : The visual world of monkeys deprived of striate cortex: Effective stimulus parameters and the importance of the accessory optic system. Vision Res. Suppl. 3, 419 — 435 (1971). P A S I K , T., and P . P A S I K : Extrageniculostriate vision in the monkey: Effect of optic chiasm section and accessory

optic system lesions. Soc. Neurosci. Abstr. I l l Ann. Meet. 184 (1973). P A S I K , T . , P . P A S I K and J . H Ä M O R I : Nucleus of the accessory optic tract. Light and electron microscopic study in normal monkeys and after eye enucleation. Exper. Neurol. 41, 6 1 2 - 6 2 7 (1973). P A S I K , T., and P . P A S I K : The visual world of monkeys deprived of striate cortex: Effective stimulus parameters and the importance of the accessory optic system. In: Visual processes in Vertebrates. Eds. T. Shipley and J . E. Dowling, 4 1 9 - 4 3 5 Pergamon, Oxford 1975. PATE, J . R . : Trans-neural atrophy of the nucleus ovoideus following eye removal in cats. Anat. Ree. 67, Suppl. 39 (1937). P A V L O V , W.: Les connexions centrales du nerf optiques chez le lapin. Le Nevraxe 1, 2 3 7 - 2 4 6 (1900). PEARSON, L . J . ,

K.J.SANDERSON

and

R.T.WELLS:

Re-

tinal projections in the ringtailed possum Pseudocheirus peregrinus. J . Comp. Neurol. 170, 227 — 240 (1976). P E R L I A , Dr.: Über ein neues Opticuscentrum beim Huhne. V. Graefes Arch. Ophthal. 35, Abt. 1, 2 0 - 2 4 (1889). P E R L I A , Dr.: Bemerkungen zur medianen Opticuswurzel beim Huhne. Neurol. Centralbl. 10, 3 9 0 - 3 9 1 (1891). P E R N K O P F , E . : Topographische Anatomie des Menschen. Vol. IV.: Topographische und stratigraphische Anatomie des Kopfes. Urban & Schwarzenberg, München, Berlin, Wien 1957. P E T R U S Z , P . : Localization and sites of action of gonadotropins in brain. In: Anatomical Neuroendocrinology Eds.: W. E. Stumpf and L. D. Grant. 1 7 6 - 1 8 4 Karger, Basel 1975. PEYRICHOUX, J . , C. W E I D N E R , J . R E P E R A N T a n d D . M I C E L I :

A experimental study of the visual system of cyprinid fish using the H R P method. Brain Res. 130, 5 3 1 - 5 3 7 (1977). P F E I F E R , R. A.: Die nervösen Verbindungen des Auges mit dem Zentralorgan. In: F. Schieck and A. Brückner. Hdb. Ophth. 1, 3 8 7 - 4 7 5 (1930). P I E C H O W I A K , H.: Das Pinealorgan. Dtsch. Med. Wochenschr. 44, 2 0 8 8 - 2 0 9 4 (1973). P O L Y A K , S.: The vertebrate visual system. Univ. Chicago Press. Chicago, III. 3 0 1 - 3 0 9 (1957). P R I B Y T K O W : Über den Sehnervenverlauf und über ihren Endigungsort in den subcorticalen Centren. Diss. (Russ.) Moskau 1895 (in: N. Tümianzew 1898). P R I N T Z , R. H . , and J . L. H A L L : A direct retinohypothalamic projection in the golden hamster. Anat. Ree. 172, 386 (1972). P R I N T Z , R. H . , and J . L. H A L L : Evidence for a retinohypothalamic pathway in the golden hamster. Anat. Ree. 179, 5 7 - 6 5 (1974). P R O B S T , M.: Über den Verlauf der Sehnervenfasern und deren Endigung im Zwischen- und Mittelhirn. Monatsschr. Psychiat. 8, 165 (1900). R A I S M A N , G.: An evaluation of the basic pattern of connections between the limbic system and the hypothalamus. Am. J . Anat. 129, 1 9 7 - 2 0 2 (1970). R A I S M A N , G.: Suprachiasmatic nuclei in relation to ovulation and circadian rhythms. Abstr. First Eurpean Neurosciences Meeting, Munich 169 (1975). R A I S M A N , G.: The reaction of synaptogenesis.in the central and peripheral nervous system of the adult rat. In: Neural mechanisms of learning and memory. Eds.: M. R. Rosenzweig and E. L. Bennett. MIT-Press, Cambridge, Mass. 3 4 8 - 3 5 1 (1976). R A L P H , C. L., and R . M. F R A P S : Long-term effects of diencephalic lesions on the ovary of the hen. Amer. J . Physiol. 197, 1 2 7 9 - 1 2 8 3 (1959a).

Accessory Optic and Retino-Hypothalamic System and R . M . F R A P S : Effect of hypothalamic lesions on progesterone induced ovulation in the hen. Endocrinol. 65, 8 1 9 - 8 2 4 (1959b).

RALPH, C. L.,

RALPH, C. L.,

D . MULL,

H . J. LYNCH

and

L. HEDLUND:

A

melatonin r h y t h m persists in r a t pineals in darkness. Endocrinology 89, 1 3 6 1 - 1 3 6 6 (1971). R A M Ó N , P. : Centros opticos de las aves. Revista trimestral micrográfica 3, 1 4 1 - 1 9 7 (1898). R A M Ó N Y C A J A L , S. : E studios talamicos. Trab. Lav. Inv. Biol. 2, 61 — 69 (1903); f r o m : Studies on the diencephalon 1 5 8 - 1 6 7 , Ed. E. Ramón-Moliner, Charles C. Thomas Pbl. Springfield, Illinois 1966. R A M Ó N Y C A J A L , S. : Textura del sistema nervoso del hombre y de los vertebrados. Tomo II, Madrid I m p r e n t a y Liberia de Nicolás Moya 1904. R A M Ó N Y C A J A L , S . : Histologie du système nerveux de l'homme et des vertébrés. Paris, A. Maloine 1909 — 1911. R E N D A H L , H . : Embryologische und morphologische Studien über das Zwischenhirn beim H u h n . Acta Zool. 5, 241 — 344 (1924). R E P É R A N T , J . : E t u d e expérimentale des projections visuelles chez la vipère (Vipera aspis). C.R. Acad. Sei. (D) (Paris), 275, 6 9 5 - 6 9 7 (1972). R E P É R A N T , J . : Nouvelles données sur les projections visuelles chez le pigeon (Columba livia) J. Hirnforsch. 14, 151 — 187 (1973). R E P É R A N T , J . : Npuvelles données sur les projections rétiniennes chez cáiman sclerops. E t u d e radio-autographique. C.R. Acad. Sei. (D) (Paris), 280, 2 8 8 1 - 2 8 8 4 (1975). R E P É R A N T , J . : The orthograde transport of horseradish peroxidase in the visual system. Brain Res. 85, 307 — 312 (1975). R E P É R A N T , J., J. P. R A F F I N et D. M I C E L I : La voie rétinothalamo-hyperstriatale chez le poussin (Gallus domesticus L.). C.R. Acad. Sei. (D) (Paris) 279, 2 7 9 - 2 8 0 (1974). R E P É R A N T , J., et J. P. R i o : Retinal projections in vipera aspis. A reinvestigation using light radioautographic and electron microscopic degeneration techniques. Brain Res. 107, 6 0 3 - 6 0 9 (1976). R E P É R A N T , J . , and M . L E M I R E : Retinal projections in cyprinid fishes: A degeneration and radioautographic study. Brain Behav. Evol. 13, 3 4 - 5 7 (1976). R E P É R A N T , J., D . M I C E L I and J.-P. R A F F I N : Transneuronal t r a n s p o r t of tritiated fucose and proline in t h e avian visual system. Brain Res. 121, 343 — 347 (1977). R É T H E L Y I , M . , and B . H A L Á S Z : Origin of t h e nerve endings in the surface zone of the median eminence of t h e r a t hypothalamus. E x p . Brain Res. 11, 145 — 158 (1970). R E T Z I U S , G. : Zur Kenntnis der lateralen Fläche des Mesencephalons und ihrer Umgebung. Biologische Untersuchungen. 8, 6 5 - 7 4 (1898). R I B A K , Ch. E . , and A. P E T E R S : An autoradiographic study of the projections from the lateral geniculate body of the rat. Brain Res. 92, 341 — 368 (1975). R I C H T E R , C. P. : Inborn nature of t h e r a t ' s 24-hour clock. J. Comp, physiol. Psychol. 75, 1 — 4 (1971). R I E K E , W . O. : Opto-hypothalamic p a t h w a y s in t h e rat. Anat. Ree. 130, 3 6 3 - 3 6 4 (1958). R I L E Y , H . A. : An atlas of the basal ganglia, brain stem and spinal cord. William and Wilkins Co, Baltimore 708 (1943). R I O C H , D . McK. : Studies on the diencephalon of the Carnivora. I. The nuclear configuration of the thalamus, epithalamus and hypothalamus of the dog and cat. J . Comp. Neurol. 49, 1 — 119 (1929a), II. Certain nuclear configurations and fiber connections of t h e subthalamus and midbrain of dog and cat. J. Comp. Neurol. 49, 121 — 153 (1929b). I I I . Certain myelinated fiber connections of the dience-

249

phalon of t h e dog (Canis familiaris), cat (Felis domestica) and aevisa (Crossarchus obscurus) J . Comp. Neurol. 53, 3 1 9 - 3 8 3 (1931). R I O C H , D . M C K . : Certain myelinated fiber tracts of t h e brain stem of the cat. Anat. Ree. 58, 188 Suppl. : 84 (1934). R I S S , W . , H . D . K N A P P and F . S C A L I A : Optic p a t h w a y s in Criptobranchus allegheniensis as revealed by t h e N a u t a technique. J. Comp. Neurol. 121, 31 — 43 (1963). Riss, W., and J. S. JAKWAY: A perspective on the fundamental retinal projections of vertebrates. Brain Behav. Evol. 3, 3 0 - 3 5 (1970). R O D E C K , H. : Die Bedeutung des Auges f ü r die postnatale Entwicklung der Regulationszentren des Wasserhaushaltes. Z. Kinderheilk. 81, 6 8 3 - 7 0 5 (1958). R Ö T H I G , P. : Beiträge zum Studium des CNS der Wirbeltiere. 8. Über das Zwischenhirn der Amphibien. Arch. f. Mikr. Anat. 98, 6 1 6 - 6 4 5 (1923). R O H E N , J. W . : Das Auge und seine Hilfsorgane. I n : H d b . Mikrosk. Anat. Eds. : W. v. Möllendorff and W. Bargmann Vol. I I I / 4 Springer-Verlag, Berlin 1964. Ross, J . : On a Case of locomotor ataxia with laryngeal crisis and one of primary sclerosis of t h e columns of Göll, complicated with ophthalmoplegia externa. Neurol. Centralbl. 5, 3 2 1 - 3 2 2 (1886). R O U S S Y , G., et M. M O S I N G E R : Annales de Médicine. 3 3 , 3 (1933). (quoted according to M. Geiringer 1938.) R O U S S Y , G., et M . M O S I N G E R : E t u d e anatomique et physiologique de l'hypothalamus. Rev. Neurol. (Paris) 61, 8 4 8 - 8 8 8 (1934). R O U S S Y , G., et M . M O S I N G E R : L'hypothalamus chez l'homme et chez le chien. Rev. Neurol. (Paris) 63, 1 — 35 (1935). R O U S S Y , G., et M. M O S I N G E R : Traité de Neuro-Endocrinologie. Masson et Cie, Paris 1946. R U B I N S O N , K.: Projections of the tectum opticum of the frog. Brain Behav. Evol. 1, 5 2 9 - 5 6 1 (1968). SAAVEDRA, J . M.,

M . PALKOVITS,

M. BROWNSTEIN

and

J. A X E L R O D : Serotonin distribution in t h e nuclei of t h e r a t hypothalamus and preoptic region. Brain Res. 77, 1 5 7 - 1 6 5 (1974). S A A V E D R A , J. M. : Localization of biogenic amine-synthesizing enzymes in discrete hypothalamic nuclei. Anat. Neuroendocrinology Int. Conf. Neurobiology of CNS-Hormone Interactions, Chapel Hill 1974, 397 — 400 (Karger, Basel 1975). S A N T I N O , D. : Contributo alio studio istologico delle connessioni dirette retino-ipotalamiche. N o t a prelim. G. ital. Oftal. 15, 3 4 8 - 3 5 9 (1962). S A W A K I , Y. : Retinohypothalamic projection: Electrophysiological evidence for t h e existence in female rats. Brain Res. 120, 3 3 6 - 3 4 1 (1977). S C A L I A , F . : Retinal projections to the olivary pretectal nucleus in t h e tree shrew and comparison with the rat. Brain Behav. Evol. 6, 2 3 7 - 2 5 2 (1972a). S C A L I A , F. : The termination of retinal axons in the pretectal region of mammals. J. Comp. Neurol. 145, 223 — 257 (1972 b). SCALIA, F . , H . KNAPP, M. H A L P E R N and W . R i s s : New observations on t h e retinal projection in t h e frog. Brain Behav. Evol. 1, 3 2 4 - 3 5 3 (1968). S C A L I A , F., and D. R. C O L M A N : Aspects of t h e central projection of the optic nerve in the frog as revealed b y anterograde migration of horseradish peroxidase. Brain Res. 79, 4 9 6 - 5 0 4 (1974). SCHEVING, L . E . ,

J. E . PAULY a n d

H . v. MAYERSBACH:

Or-

cadian r h y t h m s of physiological variables as reflected in r a t bioassay. I n : Biology D a t a Book, I l n d Ed. Vol. I I E d s . : P. L. Altman and D. S. Dittmer. Federation of

250 Mai, J . K . American Societies for Experimental Biology, Bethesda, Maryland 1 0 3 9 - 1 0 4 7 (1973). SCHEVING, L. E . : Chronobiologie — die Dimension der Zeit in Biologie und Medizin. Endeavour 35, 66 — 72 (1976). SCHNEIDER, G. E . : Retinal projections characterized by differential rate of degeneration revealed by silver impregnation. Anat. Ree. 160, 423 (1968). SCHNEIDER, H . P . G.,

D . B . CRIGHTON

and

S. M . MCCANN:

Suprachiasmatic LH-releasing factor. Neuroendocrinology 5, 2 7 1 - 2 8 0 (1969). SCHOBER, W . : Die primäre optische Projektion bei Albinoratten und pigmentierten R a t t e n . Anat. Anz. 137, 257 bis 286 (1975). SCHÜTZ, H. : Anatomische Untersuchungen über den Faserverlauf im centralen Höhlengrau und den Nervenfaserschwund in demselben bei der progressiven Paralyse der Irren. Arch. f. Psychiat. 22, 527 — 587 (1891). SCHWALBE, G. : Das ggl. oculomotorii. Jenaische Zeitschrift für Naturwissenschaft. 13, 173 — 268 (1879). SCHWALBE, G. : Lehrbuch der Neurologie. E . Besold, Erlangen 1881. SENN, D. G. : Bau und Ontogenese von Zwischen- und Mittelhirn bei Lacerta sicula (Rafinesque). Acta Anat. Suppl. 55, 1 - 1 5 0 (1968). SESTINI, F . : Su di una radiazione frontale del chiasma dei nervi ottici negli uccelli. Atti Accad. Fisiocr. Ser. X I 4, 3 3 - 3 4 (1936). SESTINI, F., e L. DONATELLI: Sulla omologia, sulla origine (sulla terminazione) e sulla probabile interpretazione funzionale del fascetto della lamina terminale negli uccelli. Rass. Studi, psichiat. 25, 501 — 525 (1936). SHANKLIN, W. M. : The centrai nervous system of Chameleon vulgaris. Acta Zool. 11, 4 2 5 - 4 9 0 (1930). SHANKLIN, W. M. : The comparative neurology of the nucleus opticus tegmenti with special reference to Chameleon vulgaris. Acta Zool. 14, 1 6 3 - 1 8 4 (1933). SHARMA, S. C.: The retinal projections in the goldfish: An experimental study. Brain Res. 39, 213 — 223 (1972). SHIMO-OKU, M. : Midbrain evoked potentials and oculomotor activity produced by optic nerve stimulation. E x p . Neurol. 42, 6 2 3 - 6 3 5 (1974). SILVER, J . : Abnormal development of the suprachiasmatic region of the hypothalamus in a strain of genetically eyeless mice (ZRDCT —AN). Anat. Ree. 187, 712 (1977). SINGER, J . ,

und

E . MÜNZER:

Beiträge

zur

Kenntnis

der

Sehnervenkreuzung. Denkschr. d. Kaiserl. Akad. Wissensch., Math.-naturwissensch. Classe, Wien 55, 163 — 182 (1889). SINGER, J . ,

und

E . MÜNZER:

Beiträge

zur A n a t o m i e

des

Centrainervensystems. (Insbesondere des Rückenmarkes) Anhang. Denkschr. d. Kaiserl. Akad. Wissensch., Wien 57, 5 8 6 - 5 9 0 (1890). SINGLETON, M . C., a n d T . L . P E E L E :

D i s t r i b u t i o n of

optic

fibers in the cat. J . Comp. Neurol. 125, 3 0 3 - 3 2 8 (1965). SIOTSUKA, R . ,

J . JOVONOVICH

and

J . A . JOVONOVICH:

In

vitro data on drug sensitivity: Circadian and ultradian corticosterone rhythms in adrenal organ cultures. I n : Chronobiological Aspects of Endocrinology Eds. J . Aschoff, F . Ceresa and F . Halberg. F . K . Schattauer Verlag Stuttgart, 2 5 5 - 2 6 7 (1974). SHIMADA, S . , M . ISHIKAWA a n d C h . T A N A K A :

Histochemical

mapping of dopamine neurons and fiber pathways in dog mesencephalon. J . Comp. Neurol. 168, 533 — 544 (1976). SMITH, A . R . ,

and

J . ARIÉNS

KAPPERS:

Effect

of

pineal-

ectomy, gonadectomy, ¿»CPA and pineal extracts on the rat parvocellular neurosecretory hypothalamic system;

a fluorescence histochemical investigation. Brain Res. 86, 3 5 3 - 3 7 1 (1975). SNYDER, S. H . , a n d R . SIMANTOV: T h e o p i a t e r e c e p t o r a n d

opioid peptides. J . Neurochem. 28, 13 — 20 (1977). So, K.-F.,

G. E . SCHNEIDER

and

D. O. FROST:

Normal

development of the retinofugal projections in Syrian hamsters. Anat. Ree. 187, 719 (1977). SOLLBERGER, A. : Biological rhythm research. Elsevier Publishing Company, Amsterdam, London, New Y o r k 1965. SOUL AIR AC, A . , e t M . L . SOULAIRAC : M o f i c a t i o n du c o m p o r t e -

ment sexuel et du tractus génital du rat maie après lésions hypothalamiques. C.R. Soc. biol. 150, 1097 — 1100 (1956). SOUSA-PINTO, A. : Electron microscopy observations on the possible retino-hypothalamicp rojection in the rat. E x p . Brain. Res. 1 1 , 5 2 8 - 5 3 8 (1970). SOUSA-PINTO, A . , a n d J . CASTRO-CORREIA: L i g h t m i c r o s c o p i c

observations on the possible retino hypothalamic projection in the rat. E x p . Brain Res. 11, 515 — 527 (1970). SPIEGEL, E . A.,

und

H . ZWEIG:

Zur

Cytoarchitectonic

der

Tuber cinereum. Arb. Neurol. Inst. Univ. Wien 22, 278 bis 295 (1917). STADERNI, R . : Di un sistema di vie nervöse aventi rapporto col chiasma, col nervo e col tratto ottico. Monit. Zool. Ital. 39 (1928). STADERNI, R . : Aspetti nuovi délia constituzione anatomica e delle connessioni del chiasma, del tratto ottico, e del nervo ottico. Monit. Zool. Ital. 47, 1 5 1 - 1 5 4 (1937). STANFIELD, B . , a n d W . M. COWAN: E v i d e n c e f o r a c h a n g e

in the retino-hypothalamic projection in the rat following early removal of one eye. Brain Res. 104, 1 2 9 - 1 3 6 (1976). STEPHAN, F . K . ,

a n d I . ZUCKER:

Rat

drinking

rhythms:

Central visual pathways and endocrine factors mediating responsiveness to environmental illumination. Physiol. Behav. 3 1 5 - 3 2 6 (1972a). STEPHAN, F . K . ,

and

I . ZUCKER:

Circadian

rhythms

in

drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc. Nat. Acad. Sei. (Wash.) 69, 1 5 8 3 - 1 5 8 6 (1972b). STEPHAN, F . K . ,

and

I.ZUCKER:

Endocrine

and

neural

mediation of the effects of constant light on water intake of rats. Neuroendocrinology 14, 44 — 60 (1974). STERZI, G. : Anatomia del sistema nervoso centrale dell'uomo. A Draghi, Padova Vol. I, 1914, Vol. I I , 1915. STETSON, M . H . ,

and

M. WATSON-WHITMYRE:

Nucleus

suprachiasmaticus the biological clock in the hamster? Science 191, 1 9 7 - 1 9 9 (1976). STILLING, J . : Medizin. Korrespondenzblatt, 1878. STILLING, J . : Über die centralen Endigungen des Nervus opticus. Archiv f. mikrosk. Anatomie 18, 4 6 8 - 4 8 0 (1880). STILLING, J . : Über einige neue Opticusverbindungen. Centralblatt für Augenheilkunde 4, 377 (1880). STILLING, J . : Über Chiasma und Tractus opticus. Verhandlungen der 6. Wanderversammlung süddeutscher Neurologen 1881. STILLING, J . : Untersuchungen über den B a u der optischen Zentralorgane. I. Teil: Chiasma und Tractus opticus. Th. Fischer, Kassel, Berlin 1882. STREIT, P . , a n d J . C. R E U B I : A n e w a n d s e n s i t i v e s t a i n i n g

method for axonally transported horseradish peroxidase (HRP) in the pigeon visual system. Brain Res. 126, 5 3 0 - 5 3 7 (1977). STRÖER, W . F . H. : Zur vergleichenden Anatomie des primären optischen Systems bei Wirbeltieren. Zeitschr. Anat. Entw.-Gesch. 110, 3 0 1 - 3 2 1 (1940).

Accessory Optic and Retino-Hypothalamic System W. F . : Estradiol-concentrating neurones : Topography in the hypothalamus by dry-mount autoradiography. Science 162, 1 0 0 1 - 1 0 0 3 (1968). S T U M P F , W. E., and M. S A R : Hormone-architecture of the mouse brain with 3 H-estradiol. Anat. Neuroendocrinology. Int. Conf. Neurobiology of CNS-Hormone Interactions, Chapel Hill 1974, 8 2 - 1 0 3 (Karger, Basel, 1975a). S T U M P F , W . E . , and M . S A R : Anatomical distribution of corticosterone-concentrating neurons in rat brain. Anat. Neuroendocinology Int. Conf. Neurobiology of CNSHormone Interactions, Chapel Hill 1974, 254—261 (Karger, Basel, 1975 b). S T U M P F , W . E . , M . S A R and D . A. K E E F E R : Atlas of estrogen target cells in rat brain. Anat. Neuroendocrinology Int. Conf. Neurobiology of CNS-Hormone Interactions, Chapel Hill, 1974, 1 0 4 - 1 1 9 (Karger, Basel, 1975). S U B U R O , A. M . , and A. P E L L E G R I N O D E I R A L D I : An ultrastructural study of the rat's suprachiasmatic nucleus. J . Anat. 105, 4 3 9 - 4 4 6 (1969). S U Z U K I , N. : The diencephalic and some other systems in Xantharpyia amplexicaudata. Proc. Koninklijke Nederlandse Akad. van Wetenschappen 39, 7 6 6 - 7 7 4 (1936a). S U Z U K I , N. : The diencephalic and some other systems in Xantharpyia amplexicaudata. Proc. Koninklijke Nederlandss Akad. van Wetenschappen 39, 881 — 887 (1936b). S U Z U K I , N . : The diencephalic and some other systems in Xentharpyia amplexicaudata. Proc. Kon. Akad. Wet. 39, 3 - 1 6 (1936). S U Z U K I , N., and S . I S I Z A W A : On diencephalic nuclei and fiber paths in the brain of Cittelus mongolicus. Jap. J . Med. Sei. Anat. 7, 1 9 3 - 2 1 0 (1938). S W A N S O N , L. W. : An autoradiographic study of the efferent connections of the preoptic region of the rat. J . Comp. Neurol. 167, 2 2 7 - 2 5 6 (1976c). STUMPF,

SWANSON, L . W . ,

W . M . COWAN

and

E. G. JONES:

An

autoradiographic study of the efferent connections of the ventral lateral geniculate nucleus in the albino rat and the cat. J . Comp. Neurol. 156, 1 4 3 - 1 6 3 (1974). S W A N S O N , L. W., and W. M. C O W A N : The efferent connections of the suprachiasmatic nucleus of the hypothalamus. J . Comp. Neurol. 160, 1 - 1 2 (1975). SZENTÂGOTHAI, J . ,

B . FLERKO,

B . MESS

and

B . HALÂSZ:

Hypothalamic control of the anterior pituitary. Akademiai Kiado, Budapest (1968). (2. Auflage 1972.) T A K E D A , T . , and K. M A E K A W A : The origin of the pretectoolivary tract. A study using the horseradish peroxidase method. Brain Res. 117, 3 1 9 - 3 2 5 (1976). T H O R P E , P. A. : The presence of a retino hypothalamic projection in the ferret. Brain Res. 85, 3 4 3 - 3 4 6 (1975). T H O R P E , P . A . , and J . H E R B E R T : The accessory optic system of the ferret. J . Comp. Neurol. 170, 2 9 5 - 3 1 0 (1976). T I E N H O V E N , A. V A N : Neurophysiological approach to photosexual relationships in birds. In: La Photorégulation de la Reproduction chez les Oiseaux et les Mammifères. Eds. : J . Benoit and I. Assenmacher. Centre Natl. Rech. Sei. Paris 2 5 8 - 2 7 5 (1970). T I E N H O V E N , A. VAN, and R . J . P L A N C K : The effect of light on avian reproductive activity. In : Handbook of Physiology, Endocrinology II, Part I, Chapter 4 D. C. Amer. Physiol. Sei., Washington 7 9 - 1 0 7 (1973). T I G G E S , J , : Ein experimenteller Beitrag zum subkortikalen optischen System von Tupaia glis. Folia primatol. 4, 1 0 2 - 1 2 3 (1966). T I G G E S , J . : Retinal projections to subcortical optic nuclei in diurnal and nocturnal squirrels. Brain, Behav. Evol. 3, 1 2 1 - 1 3 4 (1970).

251

J., and M. T I G G E S : The accessory optic system in Galago crassicaudatus (primates). Anat. Ree. 160, 441 (1968). T I G G E S , J., and M. T I G G E S : The accessory optic system and other optic fibers of the squirrel monkey. Folia primatol. (Basel) 10, 2 4 5 - 2 6 2 (1969a). T I G G E S , J., and M. T I G G E S : The accessory optic system in Erinaceus (Insectivora) and Galago (Primates). J . Comp. Neurol. 137, 5 9 - 6 6 (1969b). T I G G E S , J . , and W. K . O ' S T E E N : Termination of retinofugal fibers in squirrel monkey: A re-investigation using autoradiographic methods. Brain Res. 79, 489 — 495 (1974). T I G G E S , M., and J . T I G G E S : Retinal projection in Galago crassicaudatus (primates). Anat. Ree. 163, 274—275 (1969). T I G G E S , M., and J . T I G G E S : The retinofugal fibers and their terminal nuclei in Galago crassicaudatus (primates). J . Comp. Neurol. 138, 8 7 - 1 0 2 (1970). T I G G E S , M., and J . T I G G E S : Extracellular perivascular connective tissue space in the medial terminal nucleus of the accessory optic system in rats. Z. Zellforsch. 125, 2 8 9 - 2 9 4 (1972). T R O I A N O , R., and A. S I E G E L : The ascending and descending connections of the hypothalamus in the cat. Exp. Neurol. 49, 1 6 1 - 1 7 3 (1975). T R O I A N O , R., and A. S I E G E L : Projections of the basal forebrain in the cat. Neuroscience Abstr. Society for Neuroscience sixth Annual meeting, Toronto Canada 569 (1976). T R O Y E R , J . R., and M. G O L D S M I T H : Preliminary observations on the structural relationship of the optic pathway to the supraoptic nucleus in a hibernator. Anat. Ree. 151 (1965). TSAI, C.: The optic tracts and centres of the opossum. J . Comp. Neurol. 39, 173 — 216 (1925). T S A N G , Y. C.: Visual centers in blinded rats. J. Comp. Neurol. 66, 2 1 1 - 2 6 1 (1937). T S A N G , Y. C.: Supra- and post-optic commissures in the brain of the rat. J . Comp. Neurol. 72, 535 — 567 (1940). T Ü M I A N Z E W , N.: Beiträge zur Erforschung des Sympathicuseinflusses auf die contralaterale Pupille. Pflüger's Arch. ges. Physiol., 69, 1 9 9 - 2 4 8 (1898). T U R B E S , C.: Centripetal movement of amino acid protein complex in the visual system. Anat. Ree. 15, 427 (1965). T U R N E R , C. H.: Morphology of the avian brain. I. Taxonomic value of the avian brain and the histology of the cerebrum. J . comp. Neurol. 1, 39 — 92 (1891). T W I T T Y , V . C . : Influence of the eye on the growth of its associated structures, studied by means of heteroplastic transplantation. J . exp. Zool. 61, 333 — 374 (1932). U N G E R S T E D T , U . : Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol. Scand. 367 (Suppl.) 1 — 48 (1971). V A N D E S A N D E , F . , J . D E M E Y and K . D I E R C K X : Identification of neurophysin producing cells. I. The origin of the neurophysin-lilce substance-containing nerve fibres of the external region of the median eminence of the rat. Cell Tiss. Res. 151, 1 8 7 - 2 0 0 (1974). V A N D E S A N D E , F . , K . D I E R C K X and J . D E M E Y : Identification of the vasopressin-neurophysin producing neurones of the rat suprachiasmatic nuclei. Cell Tiss. Res. 156, 3 7 7 - 3 8 0 (1975). V A N E G A S , H., and S . O . E. E B B E S S O N : Retinal projections in the perch-like teleost Eugerres plumieri. J . Comp. Neurol. 151, 3 3 1 - 3 5 8 (1973). V A S T O L A , E . F . : Localization of visual functions in the TIGGES,

252

Mai,

J.

K.

mammalian brain: A Review. Brain Behav. Evol. 4 2 0 - 4 7 1 (1968). VINOGRADOVA, V . M . , a n d I . U . B . M A N T E I F E L : A x o n a l

1,

com-

position of the marginal and basal optic tracts of the grass frog (russ.). Neirofiziologiia 8, 54 — 61 (1976). VONEIDA, T h . J . , a n d C. M. SLIGAR: A c o m p a r a t i v e

neuro-

a n a t o m y study of retinal projections in two fishes: Astyanax hubbsi (the blind cave fish) and Astyanax mexicanus. J . Comp. Neurol. 165, 8 9 - 1 0 6 (1976). VRIEND, J . : Regulatory effects of the pineal gland on free thyroxin index of male golden hamsters. Anat. Ree. 187, 738 (1977). VULLINGS, H. G. B . : Influence of light and darkness on the hypothalamo-hypophysial system of R a n a temporaria. Z. Zellforsch. 113, 1 7 4 - 1 8 7 (1971). VULLINGS, H. G. B . : Influence of light and darkness on the hypothalamo-hypophysial system of blinded and unilaterally blinded frogs (Rana temporaria). Z. Zellforsch. 136, 3 5 5 - 3 6 4 (1973). VULLINGS, H. G. B., and J . KERS: The optic tracts of R a n a temporaria and a possible retino-preoptic pathway. Z. Zellforsch. 139, 1 7 9 - 2 0 0 (1973). VULLINGS, H . G . ,

and

A. M. HEUSSEN:

Electron

micro-

scopic observations on the retino-preoptic pathway of R a n a temporaria L. Cell Tiss. Res. 161, 1 7 7 - 1 8 2 (1975). WAGNER, J . : Über den Ursprung der Sehnervenfasern im menschlichen Gehirn. Dorpat: E . J . Karow 1862. WALLENBERG A.: Das mediale Opticusbündel der Taube. Neurol. Centralbl. 17, 5 3 2 - 5 3 7 (1898). WALLENBERG, A.: Notiz zur Anatomie des Tractus peduneularis transversus beim Meerschweinchen. Anat. Anz. 24, 1 9 9 - 2 0 0 (1904). WALLEY, R . E . : Receptive fields in the accessory optic system of the rabbit. E x p . Neurol. 17, 2 7 - 4 3 (1967). WEBER, A.: Fibres centrifuges dans le nerf optique d l'Axolotl. Schweiz. Mediz. Wschr. 75, 631 (1945). WELLS, J . , and J . SUTIN: Trigeminal and pretectal influences upon slow-wave activity of the ventral tegmental area in the cat. E x p . Neurol. 7, 355 — 365 (1963). WENISCH, H. J . : Retinohypothalamic projection in the mouse: Electron microscopic and iontophoretic investigations of hypothalamic and optic centers. Cell Tiss. Res. 167, 5 4 7 - 5 6 1 (1976)y WENISCH, H . ,

and

H . G . HARTWIG:

Karyometric

investi-

gations of the suprachiasmatic nucleus in blinded rats. Z. Zellforsch. 143, 1 4 3 - 1 4 7 (1973). WENISCH, H., a n d H . - G . HARTWIG:

Retinohypothalamische

Projektion bei R a t t e , Maus und Sperling. Verh. Anat. Ges. 69, 5 7 5 - 5 7 8 (1975). WESTHEIMER, G., and S. M. BLAIR: Unit activity in accessory optic system in alert monkeys. Invest. Ophthalmol. 13, 5 3 3 - 5 3 4 (1974). WINGSTRAND, K . G.: The structure and development of the avian pituitary. Lund, Gleerup 1951. WINKLER, C.: Opera Omnia. Bd. 6 u. 7 (Manuel de Neur. S. 37) Verlag De Erven F . Bohn, Haarlem 1918 (in: R . A. Pfeiffer, 1930).

L. Martini and W. F . Ganong. Acadcmic Press, New York, 1 9 - 5 9 (1967). WURTMAN, R . J . : The effects of light on man and other mammals. Ann. Rev. Physiol. 37, 467 — 483 (1975). YAMADA, H . : Light and electron microscopic analyses of the medial terminal nucleus of the accessory optic system in the mouse. I. Normal structure. Z. Mikrosk. Anat. Forsch. 88, 9 9 7 - 1 0 1 7 (1974). YAMADA, H . : Light and electron microscopic analyses of the medial terminal nucleus of the accessory optic system in the mouse. I I . After destruction of the eye. Z. Mikrosk. Anat. Forsch. 88, 1 1 6 1 - 1 1 7 1 (1974). ZABORSZKY, L . ,

C. S. LERANTH,

J . MARTON

M . PALKO-

ZIEHEN, T . : Das Centralnervensystem der Monotremen und Marsupialier. Semons zoolog. Forschungsreisen, Fischer, J e n a (1901). ZIMMERMAN, E . A . ,

R . DEFENDINI,

H . W . SOKOL a n d

A. G.

ROBINSON: The distribution of neurophysin — secreting pathways in the mammalian brain: Light microscopic studies using the immunoperoxydase technique. Ann. N . Y . Acad. Sci. 248, 9 2 - 1 0 9 (1976). YAGI, K . ,

a n d Y . SAWAKI: O n t h e l o c a l i z a t i o n

of

neuro-

secretory cells controlling adenohypophysial function. J . Physiol. Soc. (Japan) 32, 6 2 1 - 6 2 2 (1970). YAGI, K., and Y . SAWAKI: Medial preoptic nucleus neurons: inhibition and facilitation of spontaneous activity following stimulation of the median eminence in female rats. Brain Res. 120, 3 4 2 - 3 4 6 (1977). ZWEIG, M. H . , S. SNYDER a n d

J . AXELROD:

E v i d e n c e for

a

non-retinal pathway of light to the pineal gland of newborn rats. Proc. Nat. Acad. Sci. (Wash.) 56, 5 1 5 - 5 2 0 (1966).

The author's

adress:

Dr. Jürgen K . MAI C. und O. Vogt — Institut für Hirnforschung der Universität Düsseldorf Universitätsstr. 1 D-4000 Düsseldorf Federal Republic of Germany Acknowledgements: The author is very much indebted to Prof. Dr. A. HOPF for his generosity and encouragement. I thank Dr. T. TOBIAS for critically reading the manuscript and Miss R . HARTMANN for secretarial help.

W I N K L E R , C., a n d A . P O T T E R : G u i d e t o r a b b i t ' s b r a i n ( 1 9 1 1 ) .

Guide to cat's brain (1914) Versluys,. Amsterdam. WLASSAK, R . : Die optischen Leitungsbahnen des Frosches. Archiv f. Anat. u. Physiol., Physiol. Abtlg., Suppl. 1 — 28 (1893). WURMBACH, H . : Lehrbuch der Zoologie. G. Fischer, Stuttgart (1962). WURTMAN, R . J . : Effects of light and visual stimuli on endocrine function. I n : Neuroendocrinology, Vol. 2. Eds.

and

VITS : Afferent brainstem pathways to hypothalamus and to limbic system in the rat. I n : Hormones and brain function, Budapest 1971, 449—457. Akadimiai Kiado, Publishing House of the Hungarian Acad. Sci., Budapest 1973.

LIST OF ABBREVIATIONS A AA AAOT ACh AChE

Amphibia amino acid Tr. opticus accessorius ant. Acetylcholine — esterase

Accessory Optic and Retino-Hypothalamic System AD ADb

axodendritic synapsis — — contacting at dendritic bifurcation ADd — — contacting at distal portion of dendrite ADp — — contacting at the proximal portion of dendrite AHA anterior hypothalamic area AOS accessory optic system AOT accessory optic tract AOT (a) separation of AOS-fibres from the main (m) optic projection (POS) rostral to cgl (a) ; (p) within the geniculate area (m) ; from the BCS (p) AOT —IF accessory optic tract Fc. inferior ( H A Y H O W ) AOT —SF — — Fc. superior ( H A Y H O W ) AOTN terminal ncll. of AOS AP area praetecti APO (a, 1, m) — praeoptica (ant., lat., med.) ARG autoradiography AS axo-somatic synapsis ASC area suprachiasmatica ATV area tegmentalis ventralis ( T S A I )

HRP HTA HYP

horseradish peroxidase hypophysiotropic area hypothalamus

I Inf IP

Inhibition infundibulum inhibitory response

L

LT Lys

lesion (inside parenthesis: location where L was performed) leucine etc. indicate continuous exposure for prolonged period; lower case letters (I, d) indicate irradiation or dark period interrupting or interposed between, sustained periods of light or darkness (m: monochromatic radiation) lamina terminalis lysine

M M Mes Meth MFB

mammals MARCHi-technique midbrain methionine medial forebrain bundle

Leu LL, DD

B BCS

birds brachium colliculi sup.

N

NAUTA-technique

C. C.occ CC CO Com. CP CS CSD CSDV

cortex occipital C. crus cerebri chiasma opticum commissura Com. posterior colliculus superior Com. supraoptica dorsalis — — — pars ventralis ( M E Y N E R T )

N. NI - N X I I NCs NE

nervus cranial nerves I - X I I nn. cervicales superiores norepinephrine

DA DD

dopamine organism exposed to continuous dark degeneration [method(s)]

Deg.

EP

Excitation, Augmentation electron microscopical evaluation, study evoked potential, -response

F FAOa

fishes Fc. accessorius opticus ant.

FAOp

Fc. accessorius opticus post.

Fc. FH FO FOR FP Fuc

fasciculus fornix formatio reticularis facilitory response (potential) fucose

G GTI/II

GoLGi-technique s y n a p t i c t e r m i n a l of GRAY-type I / I I

H

haematoxylin haematoxylin-eosin hydroxyindole-O-methyl transferase

E Elmi

(BOCHENEK,

1908)

(MARBURG, 1942)

HE HIOMT

FINK-HEIMER

Hirnforschung, Bd. 19, Heft 3

253

NG

NAUTA-GYGAX-technique

NHYP

neurohypophysis

O: OKN

Origin optokinetic nystagmus

P PAOT PCG PCMA Phe PIN POS Pro

pretectum Tr. opticus accessorius post. periaquaductal gray pedunculus corp. mamillaris phenylalanine corpus pineale primary optic system proline

R Rad. RHS

reptiles radix retino-hypothalamic system

S SGC (VIII) SM SN SO SPA, SPM ST

silver impregnation techniques (if not otherwise specified) substantia grisea centralis (ventriculi III) Stria medullaris thalami substantia nigra stratum opticum of CS substantia perforata ant., med. ( K R A U S E ) stria terminalis

T TC TI TIO TN

toluidine blue tuber cinerum Tr. infundibularis — isthmo-opticus terminal ncl. (see: "1 — 6") 18

254 Mai, J. K. TO TOB TPT Tr. Try TT Tyr Til

tectum opticum Tr. opticus basalis — peduncularis transversus Tractus tryptophan Tr. tecto-thalamicus tyrosine Tr. opticus

VIII

ventriculus tertius

W

WEIL,

"X"

bundle of medial coursing, late crossing optic fibres

ZI

zona incerta

5HT

serotonin

(a) aD aot

(n) nel. nlll

newborn animal nucleus nel. originis N I I I

oa

nel. opticus accessorius = - of t h e AOS = — tr. opt. access. ( C A M P B E L L ,

ob

— basalis opticus = — Tr. optici basalis = basaler Opticuskern = nel. basalis tr. optici = nel. of t h e basal optic root (tract) nel. opticus tegmenti (TSAI) = — Tr. opticus access, tegmenti

ot

(IBRAHIM,

ar atr eglv cgm

corpus geniculatum lat., pars ventralis — — mediale

d dev dt

day (s) dense core vesicles nel. dorsalis terminalis = dorsal terminal nel. of AOS

em (d, v) ep

nel. ectomamillaris (pars dors., -ventralis) ( = SGL- ectomamillare, E D I N G E R , 1 8 9 9 ) — entopeduncularis

ges gob

ggl. cervicale sup. ggl. basale opticum

h ha hab hdm hi hp hpv hpvr hvm

hour (s) nel. anterior hypothalami — habenulae — dorsomed. hypothalami — lateralis hypothalami — posterior hypothalami — periventricularis hypothalami — periventricularis rotundocellularis — ventromedialis hypothalami

i ip i.p. ist

nel. interstitialis ( R A M Ó N Y nel. interpeduncularis intraperitoneal application ggl. isthmi

limi It

light microscopical s t u d y nel. lateralis terminalis = lateral terminal nel. of AOS m o n t h (s) pars magnocellularis eminentia mediana

minutes nel. medialis terminalis = medial terminal nel. of AOS

EBBESSON,

WEIGERT

adult animal anterograde degeneration nel. Tr. opticus accessorius = accessory optic nel. nel. arcuatus atrophy

m mc mE

min. mt

CAJAL)

1969)

SHANKLIN,-1941)

p paot pc ped pf pm (d, m) po (a, 1, m) pome pv

nel. praetectalis olivaris nel. of t h e P A O T pars parvocellularis nel. peduncularis ( B E L L O N I C I , 1 8 8 8 ) pars profunda nel. praemamillaris (dors., med) nel. praeopticus (ant., lat., med.) — — magnocellularis paraventricularis

r rD

nel. ruber retrograde Degeneration

se scp scv sevi sf si sm so sut

nel. suprachiasmaticus — —, pars posterior — —, pars ventralis — —, pars ventro-lateralis pars superficialis nel. septi lat. — — med. — supraopticus — subthalamicus

tDeg. th t h a (d) thd (1, m) thl (d, p) thm tho thp thr t h v (1) tnDeg. to tpt

terminal degeneration thalamus nel. anterior (dors.) thalami — dorsalis thalami (pars lat., med.) — lateralis thai, (pars dors., post.) — medialis thalami thalamus opticus nel. posterior thalami — reticularis thalami — ventralis thalami (pars lat.) transneuronal degeneration nel. tr. optici — tr. peduncularis transversus (v. G U D D E N ) = — fascio pedunculare transverso (CASTALDI,

1923)

= — tr. transversus pedunculi

(HERRICK,

1925)

tub

nel. tuberis

vcgl

corpus geniculatum lat., pars ventralis

w

week (s)

y

year (s)

Accessory Optic and Retino-Hypothalamic System SYMBOLS

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unilateral enucleation (or related procedures) bilateral enucleation enucleation performed at different times :* the longer surviving eye intraocular injection stimulation (of) a) site of stimulation b) site of recording surviving time (s) aberrant fibres, fibres of passage ipsilateralcontralateral, crossed pathway ipsi- and contralateral

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