Patterns of synaptic interconnections in the dorsal lateral geniculate nucleus of cat and monkey: A brief review

Vision Res. Supplement No. 3, pp. 21 l-227.

Pergamon Press 1971. Printed in Great Britain.

PATTERNS OF SYNAPTIC INTERCONNECTIONS IN THE DORSAL LATERAL GENICULATE NUCLEUS OF CAT AND MONKEY: A BRIEF REVIEW’ R. W. GUILLERY Department of Anatomy, Universityof Wisconsin,Madison, Wisconsin53706,U.S.A. 1. INTRODUCTION

THE SYNAPTICinterconnections in the dorsal lateral geniculate nucleus determine the patterns of activity that can reach the visual cortex and a knowledge of these interconnections would appear to be vital for an understanding of higher visual functions. It is curious that, at present, information about cortical visual functions is more interesting and sophisticated than knowledge of the thalamic relay that the cortex depends upon for its input. To a certain extent this situation arose because light microscopists had a relatively simple view of the geniculate relay (GLEESand LE GROSCLARK,1941;POLYAK,1957) while electrophysiological observations showed that geniculocortical activity differed only in rather subtle ways from retinogeniculate activity (e.g. HIJBELand WIESEL,1961). Electron microscopical studies undertaken during the last eight years have demonstrated an unexpected complexity of interconnections within the lateral geniculate nucleus and have shown that earlier light microscopical interpretations are quite untenable. Thus, it appears that synaptic junctions within the nucleus were never properly identified by light microscopical methods and that such an identification must depend upon electron microscopical studies. The electron micrographs, themselves, are difficult to interpret because they give no indication of the three-dimensional extent of the individual neural processes within the nucleus, nor do they show the extrageniculate origin of the individual axons. In order to arrive at an understanding of the connectivity patterns within the nucleus it is necessary to correlate the electron micrographs with light microscopical observations and with studies of the degeneration that follows extrageniculate lesions. In the following paper some light and electron microscopical observations will be summarized and related to each other as far as possible. The aim will be to show what interpretations regarding geniculate connectivity patterns are possible at present and to draw attention to some of the problems that remain to be solved before the organization of the lateral geniculate nucleus can be understood. 2. LIGHT MICROSCOPICAL STUDIES OF FIBER DEGENERATION These studies have demonstrated retinogeniculate and corticogeniculate fiber systems. Although some accounts suggest that there may be other extrinsic afferents to the lateral geniculate nucleus (STERIADEand DEMETFZXU, 1960; ARDEN and ~(JDERBERG,1961; SUZUKIand TAIRA,1961; SHUTEand LEWIS,1963), no reliable anatomical information about the termination of such fibers is available and degeneration studies have failed to demonstrate them (SZENTAGOTHAI, 1963). 1 Supported by NIH Grant ROI-NS-06662. 211

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The retirzogeniculate axons in cat and monkey”

have a laminar

distribution

organi~ecl \r

that each eye sends fibers to one set of Iaminae. Within each lamina is a retinotopicall) organized representation of a hemiretina and the representations of homonymous hcmiri. tinae are in register. That is, any single point in the visual field can activate geniculatc cells arranged along a line that passes through all the laminae. In most parts of the nucleus the\e lines of projection pass roughly perpendicular to the laminae (see WALLS, 1953; POLYAK:, 1957; HUBEL and WIESEL,1961; BISHOP,KOZAK, LEVICKand VAKKUR, 1962; LATIFSand SPRAGUE,1966; STONEand HANSEN,1966; GAREY and POWELL, 1968). The fiber and cell degeneration that occurs in the monkey indicates that the retinogeniculate axons end in the main laminae with no overlap and with no significant termination between the laminae (LE GROSCLARK,1932 ; GLEESand LE GROS CLARK, 1941; GLEES, I 961: MATHEWS, COWANand POWELL,1960). Accounts of the retinogeniculate degeneration in the cat, which vary in several details (e.g. COOK, WALKERand BARR, 1951; COHN, 1956; HAYHOW,1958 ; LATIESand SPRAGUE,1966; GAREYand POWELL,1968), have been reviewed recently (GUILLERY,1970). It was concluded that the cat resembles the monkey in having no significant interlaminar retinogeniculate termination. Most of the retinogeniculate axons are relatively coarse and all appear to be myelinated (see DONOVAN,1967). However, there is some segregation of fiber types within the nucleus. In the cat the ventral ipsilateral component (to lamina C1)3consists entirely of fine axons and in the other laminae the axons that come from the periphery of the retina tend to be slightly coarser than those arising centrally (GUILLERY,1970). Corticogenicdate axons come from areas 17, 18 and 19 in the cat and distribute to all the geniculate laminae, forming a significant part of the interlaminar plexus (BERESFORD, 1961; GUILLERY, 1967a; GAREY, JONES and POWELL, 1968). These fibers are rather fine and consequently difficult to stain, Reports that none of the corticogeniculate axons arise in area 17 or that none end in the C laminae (HOLL~NDER, 1970) are probably based on incomplete impregnations of the degenerating fibers. Material prepared recently confirms the earlier descriptions of GIJILLERY(1967a) and GAREYet al. (1968). It shows that degeneration in the C laminae can always be demonstrated after relatively large cortical lesions and that degenerating corticogeniculate axons from area 17 can be stained even after very small lesions confined to the medial aspect of the hemisphere (NIIMI, KAWAMURA and ISHIMARU, 1970; GUILLERY,unpublished observations). Corticogeniculate axons in the monkey have been less fully studied. BERESFORD (1962) showed them distributing to the parvocellular laminae after a large cortical lesion, but the details of their origin from striate or peristriate cortex or of their possible ending in the magnocellular laminae are not known. The corticogeniculate projection is organized so that retinotopically correspondent points of cortex and lateral geniculate nucleus are linked with each other (Gay et al., 1968 ; MONTEROand GUILLERY,1968). Further, in the monkey, cat and rat the corticogeniculate axons pass through the nucleus along the lines of projection so that they tend to form a plexus that is organized perpendicularly to the laminae. However, in the cat there is also a tangential distribution of these fibers between the laminae which suggests that there may be significant interaction between points representing different parts of the visual field. 2 “Monkey” will be used in the following account to refer to old world monkeys, generally Mucacus, which has been most widely used. 3 The laminar terminology suggested by GUILLERY (1970) for the cat’s nucleus will be followed throughout this account.

Synapses in Dorsal Lateral Geniculate Nucleus 3. STUDIES

OF GOLGI

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PREPARATIONS

The cell and fiber types that are shown by the Golgi methods have been studied in particular detail in the A laminae of the cat (TELLO,1904; O’LEARY,1940; SZENTAGOTHAI, 1963,1964; PETERSand PALAY,1966; GUILLERY,1966). Figure 1 is a schematic representation of some of the neural elements that can be seen in the cat in these laminae and indicates their

laminar distribution. The three retinogeniculate axons shown in the figure (RG) form a part of a much more extensive bushy terminal arborization which is oriented perpendicularly to the plane of the laminae (TELLO,1904). This generally does not impregnate well in the adult, presumably because a part of it is myelinated. Each fiber appears to distribute its terminals to a single lamina, although O’LEARY(1940) has described a few branches that distribute to interlaminar regions. These axons were previously called type II axons and are identified as retinogeniculate fibers because they can, on occasion, be traced from the region of the optic tract into the nucleus (GUILLERY,1966). The corticogeniculate fibers (CG in Fig. 1) have a quite distinctive appearance. They are mostly very fine and they give off short terminal side branches over long stretches of their course. In laminae A and Al the majority run perpendicular to the laminae, that is, along the lines of projection, but in the interlaminar zones they tend to form a plexus that runs mainly in the plane of the laminae. The individual fibers can often be traced across interlaminar borders and can be seen giving off their characteristic terminals to more than one lamina. These fibers were previously called type I axons. They are regarded as corticogeniculate because they can sometimes be traced to the internal capsule and because the pattern of fiber degeneration that is stained by the Nauta method after cortical lesions matches the distribution and the morphology of these fibers very closely (GUILLERY,1967b). It must be stressed that there are a great variety of type II axons (see GUILLERY,1966; PETERSand PALAY,1966) and that only a few can be traced to the optic tract in any one block. It is probable that future studies will need to distinguish several different groups of type II axons. These may all prove to be retinogeniculate axons but it is possible that some other afferent axons, particularly local axons, are included amongst the type II fibers (see, in particular the axon of cell 3c in Fig. 1). The type I fibers have a more uniform appearance. Since some are demonstrably corticogeniculate axons, one can reasonably argue that they all are. However, there is no proof of this at present and, since the plexus formed by the type I axons in Golgi preparations is often extremely dense, much denser than one might expect from the Nauta preparations, some of the type I axons may come from non-cortical sources. Intrageniculate axons that can be seen ramifying close to their origin from a geniculate cell are seen occasionally (see cell 3c of Fig. 1). These can be clearly recognized as intrageniculate only when they can be traced to their cell of origin. The terminal portions by themselves are not always clearly distinguishable from fine type II axons. Three main cell types are shown in Figs. 1 (1, 2 and 3a, b, c). The two labelled 1 and 2 probably represent geniculocortical relay cells because they are medium-sized or large neurons and these undergo rapid retrograde changes after cortical lesions (CHOW and DEWSON,1966). However, in the adult Golgi material the axons of these cells are generally not impregnated. Two types of geniculocortical relay cells (class 1 and 2, Fig. 1) are distinguished from each other mainly on the basis of their dendrites. One type has dendrites that commonly cross laminar borders freely and that bear few, relatively slender spines (class 1 cells). The other

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FIG. 1. Schematic representation of the major cell and fiber types seen in Golgi preparations of laminae A and Al of the dorsal lateral geniculate nucleus of the cat. Lamina A is represented at the top of the figure, lamina Al at the bottom and the dotted lines indicate the region of the interlaminar plexus between laminae A and Al. Not all of the elements aredrawn to the same scale. Most have been redrawn from GUILLBRY (1966). Three of the. cells were drawn from material kindly loaned by Dr. H. J. Ralston, III. The class 1, 2 and 3 cells are labelled (1, 2 and 3), the rethrogeniculate fibers (RG) and the corticogeniculate fibers (CC). For further details see text.

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type is slightly smaller, has dendrites that generally do not cross laminar borders and these dendrites bear prominent grape-like appendages close to their primary branching points

(class 2 cells). While the majority of medium and large geniculate cells fit into this classification there are always some that do not fit. They may appear as class 1 cells which have a few dendrites with class 2 characteristics or as class 2 cells with one or two class 1 dendrites. Thus, it may prove useful to consider the dendrites as the receptive unit of the lateral geniculate nucleus and to classify the dendrites as either class 1 or class 2. This not only recognizes that some geniculate cells have both types of dendrite but stresses that the way in which retinal afferents are related to geniculate circuitry may depend primarily upon the type of dendrite that they contact (see below). The cells shown as class 3 cells in Fig. 1 characteristically have appendages with rather long slender stalks. The number of these appendages and their complexity varies considerably from one cell to another (compare cells 3 a, b and c in Fig. 1). Sometimes these stalked appendages have a very complex structure and it then becomes difficult to distinguish the axon terminals from the dendritic stalks (see also TUMBREL, 1969; FAMIGLIETTI,1970). This difficulty is shown most strikingly by cell 3c in Fig. 1, but even in this cell the distinction between the single axon and the three dendrites is quite clear when one looks at the slender axonal origin and compares the axonal with the dendritic branching pattern. The class 3 cells are generally relatively small and the majority appear to be geniculate interneurons (GUILLERY,1966). Thus, when the axon is stained one can see that it ramifies in the neighborhood of the perikaryon (see cell 3c in Fig. 1). However, the class 3 cells probably include a number of distinct sub-types and, at present, it is not possible to conclude that all are interneurons. It is clear from previously published accounts that there are different types of interneuron in the cat’s lateral geniculate nucleus. Geniculate interneurons have been described by TELLO (1904), O’LEARY (1940) and Tij~~ij~ (1966, 1969). Tello described two types of interneuron, one larger than the other and T~MB~Lrecognized two varieties of interneuron by the extent of their axonal arborization. Sub-type a has a locally ramifying axon while sub-type b has an axon that crosses laminar borders. It remains to be determined whether the three cells shown in Fig. 1 (3 a&) represent three functionally distinct cell types or examples of a continuously varying single type of interneuron. Further, the relationship between these cells and the types described by others is not clear at present because, in my material, the class 3 cells rarely stain and their relationship to the laminae is not clearly shown. The cells and fibers that can be seen in Golgi preparations of the monkey’s lateral geniculate nucleus have been described by TABOADA(1927), POLYAK(1957) and CAMPOSORTEGA,GLEESand NEUHOFF(1968). Polyak described a variety of retinogeniculate axons and attempted to establish a relationship between the type of the retinal ganglion cell and the morphology of its geniculate terminals. While it is doubtful that this is possible with the techniques currently available, Polyak’s account is a useful reminder that retinogeniculate axons are likely to show considerable morphological variations. TABOADA (1927) and Polyak (1957) found that in the monkey all dendrites avoid the interlaminar regions. Polyak distinguished principal from association neurons and showed the latter as having long slender dendrites with varicosities and simple stalked appendages. CAMPOS-ORTEGA et al. (1968) described a similar cell (their type 3 cell) with dendrites that cross laminar borders. They also described two types of principal cell, one with grape-like “A 1 l/3 S”PP.-H

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dendritic appendages close to the perikaryon and one with relatively simple dendrites. Neither of these dendritic types was seen crossing laminar borders. 4. ELECTRON MICROSCOPICAL OBSERVATIONS 1. The main axonal types The light microscopical degeneration techniques have shown that it is necessary to distinguish two main types of extrinsic afferent fiber, the corticogeniculate and retinogeniculate axons. Studies of Golgi preparations have also demonstrated the intrageniculate axons and have shown that there are a variety of geniculate cell types, recognizable to a large extent by the morphology of their dendrites. Both methods have shown that the geniculate laminae differ from the interlaminar regions since some processes distribute only within a single lamina while others cross laminar borders freely. Each of the light microscopical observations provides a clue for interpreting the electron micrographs. However, the Golgi preparations also suggest that classifications of axons and cells are as yet incomplete and, to this extent, the interpretation of electron micrographs must also be incomplete or merely tentative. For example, it is probable that there are several different types of retinogeniculate axon and also that a number of different types of interneuron can be distinguished in the nucleus. However, in neither instance is there enough information for an electron microscopical identification of the sub-types. With suitable methods of preparation, electron micrographs of the lateral geniculate nucleus of cat and monkey show three major axon types and a number of different dendritic profiles (SZENTAGOTHAI et al., 1966; GUILLERY,1969a; JONESand POWELL, 1969 a, b; GUILLERYand COLONNIER,1970; GUILLERYand SCOTT,1970). In Fig. 2 the three axon types are shown. The large synaptic knob in the upper left part of the figure (RLP) contains rather loosely scattered, mostly round synaptic vesicles and mitochondria that have a pale matrix. Axons like this form the largest terminals in the nucleus and have been called RLP axons (round vesicles, large terminals, pale mitochondria, see GUILLERY,1969a). The largest of these axons, which are 5-6 TVacross in the cat and very much larger in the monkey, contain a core of neurofilaments. In the cat they form about 20 per cent of all the synaptic knobs. The two synaptic knobs in the lower central part of the figure contain smaller vesicles which have a more irregular, often flattened shape. For this reason they have been called F axons. The F axons have terminals that are generally 1-2 p in diameter and are never as large as the largest RLP axons. The F axons contain mitochondria that have a dark matrix and only rarely have a core of neurofilaments in the terminal. The third type of terminal in Fig. 2 belongs to an RSD axon (round vesicles, small terminals and dark mitochondria). These terminals, which form nearly 50 per cent of the terminals in the cat’s nucleus, characteristically contain rather closely packed round vesicles. Their profiles rarely exceed l-5 p in diameter and generally are I p or less. Most of the profiles show no mitochondria, but when a mitochondrion is present it has a dark matrix and resembles those seen in the F axons. The great majority of the axon terminals in the dorsal lateral geniculate nucleus of the rat, cat and monkey can be placed into one of these three categories (GUILLERY, 1969a,b; GUILLERYand COLONNIER,1970; GUILLERYand SCOTT,1970; VALDIVIA,this volume). The identification of these terminals as retinogeniculate axons (RLP), corticogeniculate axons (RSD) or intrageniculate axons (F) is discussed later. The classification is independent of these identifications and it can be clearly related to a number of rules of connectivity. These are given below.

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1. Axons that contain round vesicles always make asymmetrical synaptic junctions (see COLONNIER, 1968). However, the asymmetry is more marked at junctions made by RSD than at junctions made by RLP axons. 2. F axons generally make symmetrical synaptic junctions. Occasionally one sees an F axon that makes an asymmetrical junction. It has so far not been possible to determine whether those F axons that make asymmetrical junctions represent a distinct class in terms of their origin or connections. 3. The postsynaptic element at a geniculate synapse can be a perikaryon, a dendrite or an F axon. RLP and RSD axon terminals never form the postsynaptic element. 4. RSD axons do not contact the perikarya or the proximal dendritic segments. They end primarily upon the finest peripheral dendrites. 5. F axons contact all parts of the geniculate cell surface, while RLP axons tend to end mainly upon the dendritic segments that lie close to the perikaryon. 6. A special type of contact, the filamentous contact, which is characterized by irregular thickenings applied to the membranes and by a concentration of filamentous and tubular profiles close to the dendritic membrane (see COLONNIER and GUILLERY,1964; GUILLERY, 1967b) is commonly seen at junctions formed by RLP axons. F axons make filamentous contacts rarely, RSD axons never do so. Filamentous contacts also occur at dendro-dendritic, dendro-somatic or somato-somatic junctions but never occur at axo-axonal junctions. 2. Synaptic patterns in lateral geniculate nucleus of the cat Within the limitations set by the rules given above one can see a variety of synaptic patterns in the lateral geniculate nucleus. The A laminae of the cat have been studied in most detail and will be described first. The most striking feature of the A laminae is formed by the encapsulated synaptic zones or glomeruli (SZENTAGOTHAI,1963, 1964; SZENTAGOTHAI, HAMORIand TUMBREL, 1966; PETERSand PALAY, 1966; GUILLERY,1967b, 1969; JONESand POWELL, 1969a). Each encapsulated synaptic zone consists of many closely packed neural profiles and is partially or completely enveloped by a capsule of glial lamellae (see Fig. 3). This capsule only rarely sends a short glial extension into the zone so that the neuronal profiles within the zones are characteristically in immediate contact with each other and no non-neuronal tissue intervenes between them at all. In the sections these zones are usually 7-20 p across and often contain only one RLP synaptic knob. However, the three-dimensional extent of these zones has never been determined4 and light microscopical observations (GUILLERY,1967b) suggest that they form a continuous reticulum through each of the A laminae. Thus, it is not surprising to find some sections that show more than one RLP axon within a single encapsulated zone. In addition to the RLP axon each synaptic zone contains a number of F axons, several dendritic profiles and, occasionally, one or two RSD axons (Fig. 3). Most of the dendritic profiles represent appendages rather than stems of dendrites since many of them contain complex whorls or knots of neurofilaments (GUILLERY,1967b and Fig. 3D’), and since one does not see the groups of parallel microtubules that characterize the dendritic stems. These appendages make filamentous contacts with each other and also receive filamentous and regular synaptic contacts from the RLP and F axons. The RLP axons make synaptic contacts with the F axons and occasionally one F axon synapses with another. At such F/F 4 For this reason “glornerulus”is not a suitable name.

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synapses the presynaptic element is slightly darker than the postsynaptic element, suggesting that it may prove necessary to distinguish two types of F axon (GUILLERY, 1969a). The RSL) axonsalwayslie at the periphery of the encapsulated zones (JONESand POWELL,1969a, see Fig. 3) and there they synapse either with the dendritic appendages or with the F axons. The regions between the encapsulated zones in the A laminae of the cat have been called interstitial synaptic zones (GUILLERY, 1969a). In these regions there are a great many very fine nerve fibers running in small bundles and one finds that most of the synaptic junctions are simple axodendritic junctions made by RSD axons upon medium sized and small dendrites. These same dendrites also receive a few synapses from F axons and, in addition, there are a few synapses made by RSD upon F axons. The largest dendritic profiles in the A laminae, which lie close to the perikarya, are of two distinct types. One type receives relatively few F contacts between the cell body and the first branching point, and close to the first branching point some of these dendrites bear appendages that enter one or more encapsulated synaptic zones. The second type of large dendrite receives a mixture of RLP and F axons. The RLP axons terminate in a manner similar to that shown in Fig. 2. That is, they are not associated with many other neural processes and they are generally enveloped by glial lamellae. Occasionally they are also seen to be presynaptic to one or two F axons. In the C laminae of the cat there are relatively few encapsulated synaptic zones and more of the RLP axons end in a simple manner upon proximal dendritic segments as shown in Fig. 2. The encapsulated zones that are seen in the C laminae are usually smaller and less complex than those found in the A laminae. Much of the tissue of the C laminae resembles the interstitial zones of the A laminae. There are a great many bundles of very fine axons and the majority of these axons appear to be RSD axons (see GUILLERYand SCOTT,1970). On either side of lamina Al there is a relatively cell-free interlaminar plexus which contains a number of dendrites and axons that run parallel to the plane of the laminae. These regions have the same structure as the interstitial zones of the A laminae in that they lack RLP axons and encapsulated synaptic zones and show a great preponderance of RSD axons. 3. Synaptic patterns in the lateral geniculate nucleus of the monkey Within the six major laminae of the monkey’s lateral geniculate nucleus the RLP axons commonly form synapses upon several dendritic profiles and can be seen in contact with some F axons. The F axons also contact the dendrites and, occasionally, each other. Although the patterns of connections resemble those seen within the encapsulated zones of the cat, the arrangement of the profiles differs somewhat. Thus, in the monkey the synaptic regions associated with the RLP axons do not form such strikingly complex encapsulated synaptic zones (see GUILLERYand COLONNIER,1970)and it is not possible to make a clear distinction, such as can be made in the cat, between RLP axons that join in encapsulated zones and RLP axons that simply contact dendritic stems. Patterns similar to that shown in Fig. 4 are most commonly seen in the monkey and extensive areas of section occupied by axonal and dendritic profiles with no intervening glial separation are relatively rare. Further, the RLP axons appear to contact a greater variety of dendritic profiles. The majority are large, proximal dendritic stems. Some are quite small dendritic profiles which may be appendages as in Fig. 4 but which may also represent sections of distal dendritic segments. The rounded, grape-like dendritic appendages filled with neurofilaments that form a central feature of the encapsulated synaptic zones in the cat are seen only rarely in the monkey. The RSD axons

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are usually seen in contact with small, distal dendritic segments, sometimes with F axons. They do not associate with RLP terminals to any significant extent. The pattern of synaptic organization is very similar in all six major laminae. There is some indication that the RLP terminals are larger in the magnocellular than in the parvocellular laminae and that the larger terminals make more synaptic contacts (CAMPOSORTEGAet al., 1968 ; GUILLERYand COLONNIER,1970). The regions between the laminae resemble the interlaminar plexus of the cat in showing virtually no RLP terminals and a preponderance of synapses made by RSD axons. Two thin, small-celled laminae which lie on either side of lamina 1 have been called intercalated laminae and contain mainly small axon terminals making axodendritic and axo-axonal contacts (GUILLERYand COLONNIER,1970). These will not be considered further here since, at present, nothing is known about the axons that end in these regions. 5. THE IDENTIFICATION

OF THE NEURAL PROFILES

1. The RLP axons In the monkey (COLONNIERand GUILLERY,1964; PECCI-SAAVEDRA, VACCAREZZA and READER,1968) and in the cat (SZENTAGOTHAI et al., 1966; JONESand POWELL,1969) these axons degenerate following lesions of the optic nerve. It appears that most, or all of these axons degenerate (COLONNIER and GUILLERY,1964; SZENTAGOTHAI et al., 1966), so that one can conclude that they are probably all retinogeniculate axons. However, at present the degenerative changes do not allow one to conclude that all retinogeniculate fibers are RLP axons. Some degenerating fibers are readily identified as belonging to RLP axons (see Fig. 5) but, especially in the cat, the degenerative changes occur so rapidly that one always sees a great many degenerating profiles which cannot be identified as RLP, RSD or F axons (see Fig. 6). The RLP terminals are distributed within the major laminae but not between them in the same manner as the optic nerve terminals and in the cat they show the same laminar variation in size. That is, the RLP axons are smallest close to the optic tract (GUILLERYand SCOTT, 1970). This correspondence and HENDRICKSON’S (1969) autoradiographic study further suggest that the RLP axons form the major retinogeniculate component, and they will be treated as such in the following. 2. The RSD axons The distribution of the RSD axons, which are found not only within the major laminae but also in the interlaminar regions, corresponds to the distribution of the corticogeniculate axons, which also have a translaminar distribution. The RSD axons have small round terminals similar to those on the side branches of the corticogeniculate axons. Further, in the cat, some of the RSD axons degenerate after cortical lesions (SZENTAGOTHAI et al., 1966; JONESand POWELL,1969b; and see Figs. 7-9). While this evidence suggests that some of the RSD axons are corticogeniculate fibers, two important problems remain. The first is to establish what proportion of RSD axons are corticogeniculate axons and the second is to show whether all corticogeniculate fibers are RSD axons. The first problem arises because retrograde cell changes occur very rapidly in the lateral geniculate nucleus after cortical lesions. Since some of the geniculocortical relay cells have recurrent collateral fibers (SZENTAGOTHAI et al., 1966; PETERSand PALAY,1966; O’LEARY, 1940; POLYAK,1957) and since it is possible that the terminals of recurrent collaterals show degenerative changes before the perikaryon does, it may be that some of the

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degenerating axons seen at early stages after cortical lesions are not corticogeniculate axons at all. This possibility merits serious consideration especially since thalamocortical terminals may have the same appearance as RSD terminals (see JONESand POWELL,1970). The second problem arises because, as after retinal lesions, there are always a great many degenerating axons which cannot be definitely identified as RSD, RLP or F axons (see Figs. 7-9). 3. F axons and other axon types There is no direct evidence regarding the identity of the F axons. Since they appear to survive cortical and retinal lesions (see SZENTAGOTHAI et al., 1966) they may prove to be intrageniculate fibers. It has been shown that more than one type of F axon occurs in the nucleus (GUILLERY,1969a) but nothing is known about the origin of these types. It is possible that some of the profiles that have been regarded as F axons may prove to be dendritic (see RALSTONand HERMAN,1969; GUILLERY,1969; COLONNIERand GUILLERY, 1970; WONG, 1970; FAMIGLIETTI,1970). Thus, in the cat and monkey one occasionally sees dendrites that contain vesicles as shown in Fig. 10. Although the vesicles are generally intermediate between those seen in F axons and those in R axons (see Fig. IO), any process containing such vesicles and no ribosomes would probably be classified as an F axon. It is not clear to what extent such dendritic profiles contribute to geniculate circuitry, nor exactly what their function would be. These problems have been discussed by RALSTON(1970), WONG(1970) and FAMIGLIETTI (1970). Since some of the class 3 cells seen in Golgi preparations bear dendritic “terminals” that closely resemble axon terminals (cell 3c in Fig. l), it is not unreasonable to suppose that the two types of process might be indistinguishable in electron micrographs. However, proof of this is not available at present nor is it clear whether these two types of process should be regarded as functionally distinct. Occasionally it is possible to see axon types other than the three listed above. Extremely fine, perisomatic axons that contact the largest perikarya have been described recently in the cat (GUILLERYand SCOTT,1970). These contain round vesicles and appear to be neither RLP nor RSD axons. There are also a few large axon terminals in the cat which contain sparsely packed round vesicles and dark mitochondria (GUILLERYand SCOTT,unpublished observations). The origin of these rare axon types remains to be determined. 6. THE CONNECTIONS

OF THE GENICULATE

CELLS

The pattern of connections received by the geniculate cells is known to only a limited extent and in this brief summary only the major features can be indicated. The perikarya will be considered first, then the proximal dendrites and finally the distal dendrites. It appears that all perikarya receive relatively few synapses and that most of these are made by F axons. The F axons that make axosomatic contacts do not form a distinct population since occasionally one can see that an F axon which makes an axosomatic contact also makes an axodendritic one (see Fig. 1I), In the monkey RLP axons make some axosomatic contacts (COLONNIERand GUILLERY,1964). In the cat a few fine perisomatic axons are also seen but the RLP axons only contact perikaryal regions that are close to a dendritic origin (GUILLERYand Scorr, 1970). The cell types recognizable in Golgi preparations are not readily distinguished in electron micrographs. However, in the cat one finds that the smallest perikarya (class 3) receive only F axons while the largest (class 1) receive fine perisomatic axons and RLP axons close to the dendritic origins.

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In the cat the proximal dendritic segments, which lie between the perikaryon and the first or second branching points, are important because these seem to receive most of the retinogeniculate axons (RLP). It appears that these afferents contact class 1 dendrites directly by making simple axodendritic contacts. Commonly one or two F axons which are postsynaptic to the retinogeniculate axons and presynaptic to the dendrite are associated with this synapse. The retinogeniculate axons contact class 2 dendrites within the much more complex encapsulated synaptic zones and appear to contact the grape-like appendages here rather than the dendritic stems. There is no evidence that retinogeniculate axons contact class 3 dendrites. However, if some of the F axons should prove to be class 3 dendrites then the terminal parts of the class 3 dendrites would prove to be in receipt of a rich retinal input. In the monkey the distinction between the cell and dendrite types that are seen in Golgi preparations has not been related to electron microscopical appearances. Retinogeniculate axons make most of their contacts with relatively large dendritic profiles but also contact cell bodies and quite fine dendritic processes. In electron micrographs the finest, most distal dendritic segments cannot be assigned to any cell type, nor has it been possible to demonstrate more than a single population of distal dendritic segments in cat or monkey. In both species these dendritic segments appear to be innervated mainly by RSD axons and to a lesser extent by F axons. On the basis of the evidence that is available it must be concluded that the corticogeniculate input acts mainly upon the distal dendrites although it can also, through serial axo-axonal synapses, influence the F axons. 7. CONCLUSIONS It is clear that within the lateral geniculate nucleus there are possibilities for complex interactions between retinogeniculate, corticogeniculate, intrageniculate and, possibly, other afferent fibers. A number of classifications of cells, axons, dendrites and synaptic knobs can be established and, to a certain extent, these allow one to formulate rules of connectivity within the nucleus. In the cat one can distinguish two distinct types of relationship between the retinogeniculate axons and the geniculate cells, one being a relatively simple axodendritic synapse involving class 1 dendrites and the other being a more complex relationship that occurs in the encapsulated synaptic zones. In the monkey the contacts between retinal afferents and geniculate cells are less easily categorized, but there is no reason for thinking that they are made according to a single pattern. There are many parts of the synaptic pattern that are, as yet, unknown. We do not know how many types of F axon there are, nor do we know the precise origin of these fibers. It can be doubted that the RSD axons all represent corticogeniculate axons and we do not know the origin of some of the other, rarer axon types. Only a few of the dendritic profiles can be identified in terms of their cell type and very little is known about the extent to which intrageniculate processes spread between the laminae or across the lines of projection within a lamina. It is, therefore, too early to establish wiring diagrams for the geniculate connections. Many different schemes are possible. The information that has been presented here does, however, limit the possible schemes to some extent by indicating some of the rules of connectivity that any scheme must follow. Acknowledgement

work reported here was helped by Mrs. E.

LANGER, Mrs. B. YELK

and Mr.

G. Scott.

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R. W. GUILLERY REFERENCES

ARDEN, G. B. and SGDERBERG, U. (1961). The transfer of optical information through the lateral geniculatc body of the rabbit. In Principles of Sensory Communication (edited by W. ROSENBLITH)pp. 521-M Technology Press, Cambridge. BERESFORD, W. A. (1961). Fibre degeneration following lesions of the visual cortex of the cat. In The liisucll System: Neurophysiology and Psychophysics (edited by R. JUNG and H. KORNHLJBER). Springer, Berlin. BERESFORD, W. A. (1962). A Nauta and Gallocyanin study of the cortico-lateral geniculate projection in the cat and monkey. J. Hirnforsch. 5, 210-228. BISHOP,P. O., KOZAK, W., LEVICK,W. R. and VAKKUR,G. J. (1962). The determination of the projection of the visual field on to the lateral geniculate nucleus in the cat. J. PhysioI. 163, 503-539. CAMPOS-ORTEGA, J. A., GLEES,P. and NEUHOFF,V. (1968). Ultrastructural analysis of individual layers in the lateral geniculate body of the monkey. Z. Zellforsch. 87, 82-100. CHOW, K. L. and DEWSON,J. H., III (1966). Numerical estimates of neurons and glia in the lateral geniculate body during retrograde degeneration. J. camp. Neural. 128, 63-73. COHN, R. (1956). Laminar electrical responses in the lateral geniculate body of cats. J. Neurophysiol. 19, 317-324.

COLONNIER,M. (1968). Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscope study. Brain Res. 9, 26&287. COLONNIER,M. and GUILLERY,R. W. (1964). Synaptic organization in the lateral geniculate nucleus of the monkey. Z. Zellforsch. 62, 333-355. COOK, W. H., WALKER,J. H. and BARR, M. L. (1951). A cytological study of transneuronal atrophy in the cat and rabbit. J. camp. Neural. 94, 267-292. DONOVAN, A. (1967). The nerve fiber composition of the cat optic nerve. J. Anat., Land. 101, l-l 1. FAMIGLIET~I,E. V., Jr. (1970). Dendro-dendritic synapses in the lateral geniculate nucleus of the cat. Brain Res. 20, 181-192.

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JONES,E. G. and PO~LL, T. P. S. (1969a). Electron microscopy of synaptic glomeruli in the thalamic relay nuclei of the cat. Proc. R. Sot. B 172, 1%-171. JONES,E. G. and POWELL,T. P. S. (1969b). An electron microscopic study of the mode of termination of cortico-thalamic fibers within the thalamic relay nuclei of the cat. Proc. R. Sot. B 172, 173-185.

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JONES,E. G. and POWELL,T. P. S. (1970). An electron microscopic study of the laminar Pattern and mode of termination of afferent fiber pathways in the somatic sensory cortex of the cat. Phil. Trans. R. SW., Lond. B 257,45-62. LATIES, A. M. and SPRAGUE,J. M. (1966). The projection of optic fibers to the visual centers in the cat. J. camp. Neural. 127, 35-70. LE GROSCLARK, W. E. (1932). A morphological study of the lateral geniculate body. Bv. J. OphthnImoL 16, 264-284. MATTHEWS, M. R., COWAN,W. M. and POWELL,T. P. S. (1960). Transneuronal degeneration in the lateral geniculate nucleus of the macaque monkey. J. Anat., Lond. 94, 145-l 69. MONTERO,V. M. and GUILLERY,R. W. (1968). Degeneration in the dorsal lateral geniculate nucleus of the rat following interruption of the retinal or cortical connections. J. camp. Neural. 134, 211-242. NIIMI, K., KAWAMURA,S. and ISHIMARU,S. (1970). Anatomical organization of corticogeniculate projections in the cat. Proc. Jap. Acad. 46,877-883. O’LEARY,J. L. (1940). A structural analysis of the lateral geniculate nucleus of the cat. J. camp. Neurol. 73, 405430. PECCISAAVEDRA,J., VACCAREZZA,0. L. and READER,T. A. (1968). Ultrastructure of cells and synapses in the parvocellular portion of the cebus monkey lateral geniculate nucleus. Z. ZeNforsch. 89, 462477. PETERS,A. and PALAY, S. L. (1966). The morphology of lamina A and Al of the dorsal nucleus of the lateral geniculate body of the cat. J. Anat., Lond. 100, 451486. POLYAK,S. (1957). The Vertebrate Visual System. Chicago University Press, Chicago. RALSTON,H. J., HI (1970). Presynaptic dendrites: Evidence for their existence and a proposal for their mechanism. Nature, Lond. 230, 585-587. RALSTON,H. J., III and HERMAN,M. M. (1969). The tine structure of neurons and synapses in the ventrobasal thalamus of the cat. Brain Res. 14, 77-97. SHUTE,C. C. D. and L~wrs, P. R. (1963). The cholinergic corticopetal radiations of the forebrain. J. Anat., Lond. 97,476. STERIADE,M. and DEMETRESCU, M. (1960). Unspecific system of inhibition and facilitation of potentials evoked by intermittent light. J. Neurophysiol. 23, 602-617. STONE,J. and HANSEN,S. M. (1966). The projection of the cat’s retina on the lateral geniculate nucleus. J. camp. Neurol. 126,601-624. SUZUKI, H. and TAIRA,N. (1961). Effect of reticular stimulation upon synaptic transmission in cat’s lateral geniculate body. Jap. J. Physiol. 11, 641655. SZENTA~~~HAI,J. (1963). The structure of the synapse in the lateral geniculate body. Acta Anat. 55, 166185. SZENTAGO-~HAI, J. (1964). The use of degeneration methods in the investigation of short neuronal connections. In Degeneration patterns in the Nervous System (edited by M. SINGERand J. P. SCHADE)Progress in Brain Research, Vol. 14, pp. l-32. Elsevier, Amsterdam. SZENTP;GOTHAI, J., HAMORI,J. and T~~MB~L,T. (1966). Degeneration and electron microscope analysis of the synaptic glomeruli in the lateral geniculate body. fip. Bruin Res. 2, 283-301. TABOADA,R. P. (1927). Note sur la structure du corps genouille exteme. Trab. Lab. Invest. Biol. Univ. Madrid 25, 319-329. TELLO, F. (1904). Disposition macro&pica y estructura de1 cuerpo geniculado externo. Trab. Lab. Invest. Biol. Univ. Madrid 3, 39-62. TSMB~L, T. (1966). Short neurons and their synaptic relations in the specific thalamic nuclei. Brain Res. 3, 307-326. T~MB~L, T. (1969). Two types of short axon (Golgi 2nd) intemeurons in the specitic thalamic nuclei. ~cro morph. acad. sci. Hung. 17, 285-297. WALLS,G. L. (1953). The lateral geniculate nucleus and visual histophysiology. Univ. Calif. PubI. Physiol. 9, l-100. WONG, M. T. T. (1970). Somato-dendritic and dendro-dendritic synapses in the squirrel monkey lateral geniculate nucleus. Brain Res. 20, 135-l 39. Abstract-Electron micrographs of the dorsal lateral geniculate nucleus of cat and monkey demonstrate three major axon types. With suitable fixation each type shows a characteristic preservation of organelles. One type has large terminals which contain round vesicles and pale mitochondria (RLP axons) ; the second type also contains round vesicles but has small terminals and dark mitochondria (RSD axons); while the third type contains flattened vesicles (F axons). This classification is valid in terms of connections. Comparisons with Golgi sections and with fiber degeneration studies allow tentative identification of RLP as retinogeniculate, of some RSD as corticogeniculate, and of F as intrageniculate axons. Further, several “connectivity rules” that apply to both species and all laminae can be formulated. For example: RSD axons do not make axosomatic contacts; postsynaptic elements are either dendrites of F axons, never RLP or RSD axons.

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R. W. GUILLERY In addition to these major axon types other presynaptic profiles are recognizable occasionally. These include dendrites which contain synaptic vesicles and very fine axons that contact the largest perikarya. Differences between species and between laminae are seen in terms of the part of the geniculate cell that receives the retinogeniculate input and in terms of the complexity of the synaptic zones associated with the retinogeniculate contacts.

Resumen-Electromicrofotografias obtenidas de1 nucleo geniculado laterodorsal, de1 gato y de1 mono, revelan la existencia de tres tipos principales de axones. Con la fijacion apropiada,cada tipo muestra la estructura caracteristica de sus organelas. Un tipo de axon tiene terrninales grandes, 10s cuales contienen vesiculas sinapticas redondas y mitocondrias palidas (axones RLP) ; el segundo tipo tambien presenta vesiculas redondas, pero sus termmales son pequenos y las mitocondrias son obscuras (axones RSD) ; mientras que el tercer tipo se caracteriza por tener vesiculas aplanadas (axones F). Esta clasificacion es valida en terminos de cone&ones. El estudio comparative con 10s metodos de coloration de Golgi y de fibras en degeneration nos permite hater una identification tentativa de 10s axones RLP coma retinogeniculados, de 10s RSD coma corticogeniculados y de 10s F coma axones intrageniculados. Aun mas, se pueden formular varias “reglas de conectividad” aplicables a ambas especies y a todas las laminas. Por ejemplo, 10s axones RSD no establecen contactos axosomaticos y sus elementos postsinapticos son dendritas o axones F, nunca axones RLP o RSD. Al lado de estos tres tipos principales de axones otras estructuras presinapticas pueden ser reconocidas, entre las cuales se encuentran dendritas que contienen vesiculas sinapticas y axones muy finos que contactan con el pericario de las neuronas mas grandes. Diferencias entre especies y entre laminas son reconocidas cuando se estudia el segment0 de lacelula geniculada que recibe 10s aferentes retinogeniculados y cuando se habla en terminos de complejidad de las zonas sinapticas asociadas con 10s contactos retinogeniculados.

PLATE 1 FIG. 2. This figure shows the three main axon types, RLP, F and RSD seen in the lateral geniculate nucleus (see text), from lamina A of the cat. D, dendrites; G, glial lamellae. Notice that the RLP axon is surrounded by the glial lamellaeand that this is quite unlike the situation illustrated in Fig. 3, where the RLP axons are almost completely surrounded by other neuronal protiles and isolated from the glia.

FIG. 3. Parts of two of the encapsulated synaptic zones that characterize laminae A and Al of the cat are shown. A great many F axons are seen but only some are labelled. RSD and RLP axons have also been labelled. D, dendrites; D’, grape-like dendritic appendages which contain nests of neurofllaments. G indicates the glial lamellae that tend to form a more or less complete envelope around these synaptic zones.

Synapses in Dorsal Lateral Geniculate Nucleus

FIG. 4. An RLP synaptic knob from one of the parvocellular laminae of the monkey is shown together with profiles of associated dendrites (D) and F axons. One of the dendrites gives off a slender dendritic spine (Ds). Two other protiles, which may also represent dendritic spines, are labelled X. G, glial process; nf, core of neurofilaments in the RLP axon. FOG. 5. A degenerating retinogeniculate synaptic knob in lamina A of the cat, obtained four days after removal of the contralateral eye. This axoncan be identitied as an RLP axon because it lies within an encapsulated synaptic zone, because it is presynaptic to several F axons and because the synaptic junctions that it makes are asymmetrical (unlabelled arrows). Many of the degenerating synaptic knobs seen in this material can be identified as RLP axons on similar criteria. See, however, Fig. 6. D, dendrite.

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Pro. 6. A degenerating retinogeniculate synaptic knob obtained from lamina A of the cat four days after section of the comralateral optic nerve. This degenerating knob lies at theperiphery of an encapsulated synaptic zone and cannot de6nitely be identlikd as an RLP, an RSD or an F axon. The synaptic speciaktion (u&belled arrow) is cut obliquely and neither its polarity nor its type can be determined. PIG. 7. Several fragments of degenerating axons after a large lesion of the ipsilateral visual cortex. axons and it is distributed predominan tly in the most of the corticogeniculate &em are likely to unlabelled arrows show

from lamina A of the cat obtained four days The degeneration appears to involve very tine interstitial zones. Thus one can conclude that be IUD axons. (See also Pigs. 8 and 9.) The degenerating axons.

PIG. 8. Two degenerating synaptic knobs (unlabelled arrows) from lamina A of thecat, obtained four days after a large lesion of the ipsilateral visual cortex. The lower knob appears to be making an asymmetrical synapse but the upper synapse cannot be regarded as asymmetrical.

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FIG. 9. Degenerating axons in lamina A of the cat four days after a large lesion of the ipsilateral visual cortex. On the left a degenerating synaptic knob makes an asymmetrical synaptic contact with an F axon at the periphery of an encapsulated synaptic zone. On the right a small fragment of degenerating axoplasm is seen within the synaptic zone, an unexpected site for an RSD axon. FIG. 10. A large dendrite from lamina C of the cat. This dendrite contains a number of vesicles

in the left part of the figure. The unlabelled arrows show that it makes a symmetrical synaptic junction with another dendrite. Notice that these dendritic vesicles are less regular in shape than those in the RSD axons, but more regular than those in the F axon. Frc. 11. Anaxosomaticsynapsefromlamina Cofthecat. Notice that this F axon synapses upon the cell body (lower arrow) and upon a fine dendrite (upper arrow).

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