Triadic synaptic arrangements and their possible significance in the lateral geniculate nucleus of the monkey

Brain Research, 80 (1974) 379-393

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© Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

T R I A D I C S Y N A P T I C A R R A N G E M E N T S A N D T H E I R POSSIBLE S I G N I F I C A N C E IN T H E L A T E R A L G E N I C U L A T E N U C L E U S OF T H E M O N K E Y

JOZSEF H/~MORI, TAUBA PASIK, PEDRO PASIK AND JANOS SZENT/~GOTHAI Dept. of Neurology, Mount Sinai School of Medicine of the City University of New York, New York, N.Y. 10029 (U.S.A.) and First Dept. of Anatomy, Semmelweis Univ. Medical School, Budapest IX (Hungary) *

(Accepted July 4th, 1974)

SUMMARY

Electron microscopic examination of the lateral geniculate nucleus in monkeys reveals the consistent occurrence of triadic synaptic arrangements where a retinal axon terminal is presynaptic to both a principal cell (P-cell) and a non-axonal portion of an interneuron (I-cell) containing flattened vesicles, which in turn is presynaptic to the same P-cell element. These 'triads' are found within glomeruli where the P-cell participates with a dendritic protrusion and the 1-cell with a dendritic appendage (type 1 triad), and also outside the glomerulus where the P-cell is represented by its soma or very proximal dendrite (type 2 triad), or the 1-cell profile is the soma which again contains synaptic vesicles (type 3 triad). The most parsimonious interpretation of the functional significance of the triadic synapse is to consider it as a device for the inhibitory phasing of the P-cell discharge resulting from the release of I-cell inhibitory transmitter by excitation of the interneuron through the same retinal afferent which causes the initial tonic activity of the P-cell. Further roles of the I-cell are discussed on the basis of a model which considers a random geometry of dendritic (long) and axonal (short) arborizations. The model suggests 3 possible I-ceU actions: (1) local inhibition limited to the triadic arrangement; (2) inhibition at a distance through an axonal mechanism; and (3) inhibition at a distance by way of the presynaptic dendrites.

INTRODUCTION Recent developments in synaptic ultraarchitectonics have disclosed the frequent occurrence o f stereotyped combinations of synaptic terminals which are con* Reprints available from the Mount Sinai School of Medicine.

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stant with respect to both the various types of participating elements and the polarity of the contacts. Such complex synaptic arrangements have been found in almost all parts of the central nervous system, albeit with some preponderance in the sensor~ subsystems. A newly recognized feature of these synaptic arrays is the dendritic nature of numerous profiles previously considered as axonal elementsS,l",ta, 1'~',17,:~s. The 'presynaptic' character of the dendritic terminals can, thus far, be inferred only on the basis of certain ultrastructural criteria, i.e. the presence of synaptic vesicles and their accumulation at contact sites opposite to the 'postsynaptic membrane thickening'. Although, for the time being, these 'dendro-dendritic synapses' cannot be linked directly to any functional correlate, the material available suffices to shatter the classic concept of the histodynamically polarized neuron with purely 'receptive' dendrites and 'effector" axons. However, presynaptic dendrites, as well as presynaptic somata, appear to be confined to Golgi type II interneurons, whereas the Golgi type l neuron still conforms to the classic picture. Another basic characteristic in certain of these synaptic complexes is the frequent combination of 3 contacts: (i) specific afferent terminal to relay cell dendrite; (ii) specific afferent terminal to Golgi type II cell dendrite; and (iii) Golgi type II cell dendrite to relay cell dendrite. This synaptic 'triad 's has already been observed in the earliest electron microscopic studies on the complex glomerular synapses of the sensory relay nuclei of the thalamus, including the geniculate nuclei 19,26,34. However, the recognition according to the origin of the several presynaptic and postsynaptic profiles was too uncertain to draw conclusions on the neuronal connectivity resulting from such arrangements. This situation has now changed due to the most recent findings, mainly in the L G N s,17,33 and in the MGN ~, which suggest certain generalizations particularly referable to the triadic combinations. Although some of the identifications may still be controversial, the various synapsing profiles can presently be labeled according to their presumed nature. The neuronal elements that are recognized unequivocally in electron micrographs are: (1) somata, dendrites and dendritic protrusions of the relay or principal neurons (P-cells); (2) somata, dendrites and dendritic appendages of Golgi type 11 interneurons (I-cells); (3) retinal or other specific sensory afferents; and (4) cortical afferents. Considerable uncertainty remains in the identification of l-cell axon terminals, recurrent axon collaterals of P-cells 3G, and other axons ofextrageniculate origin (perigeniculate nucleus 3e, reticular formation'-'). The present investigation attempts to concentrate on the issue of the 'triadic' combinations mentioned above. Although the material upon which these considerations are based derives from the lateral geniculate nucleus (LGN) of the monkey, it must be emphasized that most of the findings and discussion apply with minor modifications to the LGN of other mammals, to other extrinsic thalamic masses (medial geniculate, ventralis posterior lateralis), and, surprisingly, even to some intrinsic nuclei of the thalamus 11 as well. MATERIAL AND METHODS

Six normal monkeys (Macaca mulatta), ranging in weight from 2.1 to 4.6 kg,

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were perfused under deep pentobarbital anesthesia through the left ventricle with a fixative mixture of 1 ~ paraformaldehyde and 1 700glutaraldehyde, buffered to pH 7.3 with 0.4 M phosphate solution. Details of the perfusion technique and quantities utilized have been given earlied 7. The aldehyde-fixed blocks were washed in buffer, postfixed in 2 ~ buffered osmium tetroxide and embedded in Epon. Thin sections were contrasted with uranyl acetate and lead citrate, and examined in the Hitachi liE, Hitachi 12A or JEM 100B electron microscopes. RESULTS

Three types of triadic synapses Three types of triadic synaptic arrangements can be recognized in the monkey LGN. (1) The most usual by far, is the triadic coupling found in the glomeruli (Fig. 1). The specific retinal afferent contacts both a dendritic protrusion of a P-cell and a dendritic appendage of an I-cell; the latter in turn is presynaptic to the same P-cell profile. The retinal afferent has been identified in the early studies on monkey LGN 3 and named RLP terminal because of its round vesicles, and large size pale mitochondria with wide intercrestal spaces. These elements characteristically degenerate after eye enucleation. The dendritic protrusions of P-cells are characterized by the frequent occurrence of numerous filaments and of desmosomoid junctions with the retinal terminal and other P-cell dendritic profiles. They often send spine-like secondary processes into the retinal ending (Fig. lb). These features of the retinal afferents and P-cell dendrites have been recognized and correctly interpreted since the earliest studies on synaptic ultrastructure of the LGN, so that a long list of references need not be repeated here. A further proof of the identity of P-cell dendritic profiles is provided by their total disappearance after chronic ablation of the visual cortex 17 as a consequence of the process of retrograde degeneration. The subsynaptic material attached to the postsynaptic membrane is maximally developed in the retinal-P-cell synapse and minimally present in the I-cell-P-cell contact. The third element of the triadic unit was described originally as axonal on the basis of the presence of synaptic vesicles. As already mentioned in the Introduction, these terminals are, in fact, dendritic. The presence of flattened or pleomorphic synaptic vesicles in dendrites and even in the somata of I-cells has been shown repeatedly7,13,22,3s, and the identification of these profiles as belonging to Golgi type II cells has been ascertained by serial reconstructionss,13 and the survival of similar elements after chronic ablation of the entire visual cortex 17. The dendritic terminals containing synaptic vesicles are rather large (up to 3/~m) and match closely the bulbous appendages characteristic of the dendritic tree of l-cells in Golgi preparations 17. Quite frequently these profiles contain free ribosomes, cisternae and, when belonging to proximal portions of the dendrite, a few strands of rough endoplasmic reticulum. (2) It has been argued that P-cell somata may be contacted occasionally by retinal afferentslo. Although this is exceptional in the cat, such an arrangement can be observed quite frequently in the monkey. Fig. 2 shows examples of this array in

Fig. 1. Type 1 triads, a: glomerular complex with retinal axon terminal (R) in the center, presynaptic to a P-cell dendritic protrusion (Dp) and to an I-cell dendrite (Id) containing flattened or pleomorphic synaptic vesicles. Note also the presence of an axon terminal of cortical origin (Co) and of an unclassified axon ending (A) in the periphery of the glomerulus, b: synaptic triad from a glomerular complex showing the same connectivity as in (a). A spinous process (Sp) emerging from the P-cell dendritic protrusion is postsynaptic to both R and Id profiles, R being also presynaptic to Id. Scales: 1 t~rn except where indicated.

Fig. 2. Type 2 triads, a: triadic arrangement where the P-cell participates with the soma (P) which is postsynaptic to the two other elements of the triad, namely the retinal afferent (R) and the I-cell dendrite (Id). R is also presynaptic to Id. b: higher power view of area outlined in (a). c: another example of type 2 triad with participation of P-cell soma. Scales: 1 /~m except where indicated.

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Fig. 3. Type 3 triad, a: Golgi interneuron or I-cell with characteristic light perikaryon, poor in organelles containing a cluster o f synaptic vesicles (arrow) in a presynaptic position to a contacting dendritic element, b: higher power view o f the area indicated by arrow in (a). l-cell soma (1) is presynaptic to a P-cell dendritic protrusion (Dp) at ringed arrow. A large retinal terminal (R) makes contact with the same protrusion and there is also a suggestion of a similar contact between the R ending and the l-cell soma (dashed arrow). Scales: 1 /~m except where indicated.

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which the identity of the cell bodies as belonging to P-cells can be recognized easily on the basis of the rich smooth and rough endoplasmic reticulum and abundance of other organelles (see for comparison the I-cell soma of Fig. 3). The main point of interest, however, is that here the retinal terminal is also presynaptic to an I-cell dendrite containing synaptic vesicles which in turn is presynaptic to the same P-cell soma. Hence, the combination of profiles is essentially the same as in the more usual case of the 'glomerular triad', except that the P-cell is represented by its soma instead of a dendrite or dendritic protrusion. The occasional triads on very proximal portions of P-cell dendrites are included in this group. (3) The third type of triadic synapses is depicted in Fig. 3. A low power view (a) illustrates the overall configuration and the small pale cell with few rough-surfaced endoplasmic cisternae which is interpreted as an I-cell on the basis of the criteria proposed by Lieberman la. A higher power view (b) shows that the I-cell soma has a well defined accumulation of ovoid, somewhat pleomorphic, small synaptic vesicles opposite to an attachment to a dendritic protrusion of a P-cell. The retinal afferent makes a synapse with the same protrusion and there is a suggestion of a synaptic contact also with the I-cell soma, as evidenced by the accumulation of vesicles and the interruption of the glial lamella between the two elements. It should be emphasized that this type of combination is very infrequent in the monkey LGN. I-cell axons

Axons of the two main types of I-cells recognized in Golgi preparations of monkey L G N (see Discussion) have been seen as short, thin and varicose processes arborizing in the immediate vicinity of the neuronal body 17. A most important consideration for interpreting the electron micrographs is the great numerical disproportion between the terminal enlargements of the poorly arborizing axon and the immense number of dendritic appendages present in at least one of the types of 1-cells. It follows that the vast majority of terminal profiles of I-cells should be dendritic and only a small minority axonal. This indeed happens to be the case. Fig. 4a and b documents a process originating from a neuron which conforms to the criteria for 1-cells. The profile is recognized as the axon hillock and initial segment of the axon on the basis of the fascicular distribution of microtubules and the dense undercoating of the plasma membrane 20. A clear electron microscopic identification of axon terminals of I-cells, however, is difficult. The criteria suggested by Famiglietti and Peters 8 are probably the best for the time being: (i) exclusively presynaptic nature of the terminal; (ii) density and even distribution of small, flattened (or pleomorphic) vesicles; (iii) lack of ribosomes (and of endoplasmic sacs); and (iv) concave (or at least not convex) surface of the terminal at the site of the contact. To these, we may add the size of less than 1 #m. An example of such an element is given in Fig. 4d. This profile conforms to all the criteria outlined above and also shows the regular varicosities seen in Golgi preparations 17. Other synapses on interneurons

In addition to the retinal afferents, I-cell profiles can be postsynaptic to (i)

Fig. 4. a: Golgi interneuron with emerging axon indicated by arrows, b: enlarged portion of (a) showing axon initial segment with fasciculation of microtubules and dense undercoating of the membrane, c: serial synapse between two 1-cell profiles. A dendrite (Id) is presynaptic to another 1-cell element (I) which also contains vesicles, d : thin process containing synaptic vesicles and rnicrotubules, and exhibiting 3 varicosities. This profile is interpreted as an interneuron axon (la) due to its thin caliber and its exclusive presynaptic location. D, P-cell dendrite; R, retinal terminal. Scales: t /~m except where indicated.

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other I-cell elements, (ii) endings of corticofugal fibers, and (iii) axon terminals of unknown origin. (i) Synaptic contacts between I-cells are seen in the normal L G N (Fig. 4c) as well as after chronic cortical ablation iv. Synapses between two types of seemingly axonal profiles containing flattened vesicles have been observed already and designated as F1 and F2 terminals 1°. The F1 type can now be identified with some probability as belonging to an I-cell axon, and the F2 with certainty as an I-cell dendrite. It appears, therefore, that the contacts between I-cells are, at least in part, axodendritic. However, dendrodendritic synapses also occur, as expected from the apparent equivalence of synaptic sites in dendrites and somata of I-cells which is evident in the 3 types of triadic combinations described above. (ii) It has long been known that axons of cortical origin terminate in the thalamic and geniculate relay nuclei, so that it is not necessary to list the extensive literature on this subject. A type of non-retinal axon terminal was observed in earlier ultrastructural studies on the L G N 3,27,34 and its cortical origin was suggested then on the basis of degenerative changes after cortical ablations a4. This ending can now be identified safely by electron microscopic criteria and it has been labeled accordingly, by Guillery 1°, as an RSD terminal for its round synaptic vesicles, and small size dark mitochondria. In the monkey, these terminals are cup-like or cuff-like in shape, and usually devoid of mitochondria. They are more abundant in the general neuropil where they contact P-cell dendrites and, occasionally, somata (unpublished observations). Less frequently, synapses are made with I-cell dendrites as well. These axons o f cortical origin are also found in the glomeruli or encapsulated zones of the monkey (Fig. la) and cat 84. They are not involved in any way in the triadic arrangements. Off) There are several types of unidentified axon terminals, both within and without the synaptic glomeruli, that correspond in ultrastructural criteria neither to retinal afferents nor to descending cortical fibers. They do not degenerate upon either transection o f the optic nerve or short term removal of the visual cortex, and their relatively large size separates them from presumable I-cell axons. Many of them contain flattened or pleomorphic vesicles and are presynaptic to I-ceil dendrites. Although some of these terminals may represent input from the reticular formation 2, the pars ventralis of the LGN16, 32 and/or recurrent collaterals of P-cell axons 3~, their identification must be left open. Since all of these elements and also the well defined axons of cortical origin do not participate in the triadic combinations, they will not be considered in the following discussion. DISCUSSION

The triadic synaptic arrangement appears to be a fundamental ultraarchitectonic feature of the geniculates as well as of other sensory thalamic nuclei. The identification of the three principal elements involved is quite clear in all mammalian species so far investigatedS,t2,13,17. There is one axonal component which is the specific sensory afferent, and two non-axonal elements represented by the relay or principal (P-) cell, and the Golgi type II (I-) cell. The main point of general interest emerging

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from the present observations is the inescapable conclusion that, while the identity of the three participating elements is rigidly maintained, the surface region of the two cell types involved is interchangeable, i.e. it may be either the soma, a dendrite or a dendritic appendage. An additional feature which calls for functional interpretation is that the specific sensory terminal contacting the principal cell is accompanied by a third element which is a non-axonal process of an interneuron. The latter profile is constantly postsynaptic to the specific afferent and presynaptic to the P-cell, thus establishing a triadic unit. Finally, the vesicles found in every location within the 1-cell, i.e. the soma, axon, dendrites and particularly the dendritic appendages, are of the type found very generally in inhibitory neurons 37, namely small, pleomorphic, and often ovoid or elongated. This suggests that the I-cells of the sensory relay nuclei are chiefly of an inhibitory character. Such a conclusion is supported by a great host of physiological observations on the inhibitory role of Golgi type ii interneurons in other areas of the central nervous system '~,~. The functional significance of the synaptic triad in the LGN has been variously interpreted. Earlier speculations ls,30 on what were thought be to 'axo-axonic' contacts in the synaptic glomeruli, considered a mechanism of presynaptic 'disinhibition' of P-cells exercised by retinal afferents blocking the release of inhibitory transmitter of the l-cell axon terminal. This interpretation was, in fact, derived from the concept of presynaptic inhibition as proposed by Eccles 5. The identification of the profile, which is postsynaptic to the retinal afferent and presynaptic to the P-cell dendrite, as an l-cell dendrite did not necessarily negate such a mechanism, as was in fact proposed recently by Le Vay 12. However, there is little correlation between morphologic findings and neurophysiologic data on presynaptic'inhibition'. I n at least two locations where this process was described physiologically: in the synapses of primary afferents with motoneurons and with neurons of Clarke's column, it was found that the presynaptic profile in the 'axo-axonic' contact contained flattened vesicles, suggesting an inhibitory transmitter4, 24. This is not easily reconciled with the observation of primary afferent depolarization as the basis for presynaptic inhibition, since depolarization is associated with an excitatory mediator. Yet, in the case of the LGN, the retinal afferent, which is most probably excitatory, could effect a partial depolarization of the I-cell membrane. A more parsimonious explanation, however, would consider the action of the retinal afferent on the I-cell presynaptic dendrite as traditional excitation. Thereafter, the interneuron would cause a classic postsynaptic inhibitory response in the P-cell. Thus, the triad can be interpreted as a device to rapidly change the depolarization of the P-cell membrane, caused by the incoming impulse through the specific afferent, into hyperpolarization. The latter action would be triggered by the excitation of the l-cell through the same retinal afferent resulting in the release of inhibitory transmitter in close vicinity to the excitatory contact on the P-cell. In other words, the triad would be instrumental for the transformation of the tonic response of the P-cell to a retinal (or other specific) afferent volley into a phasic activity. Such a transformation is actually very generally observed in all specific thalamic nuclei 1,'~1. Further roIes of the interneurons should consider the possibility of a meaning-

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Fig. 5. Neuronal connectivity model of the LGN based on random geometry of interneuron processes. Retinal afferents and P-cells in open contour; I-cells in solid black. A cluster of retinal terminals is shown in contact with P-cell dendrites in the center of the diagram. The dendritic appendages associated with this synapse belong to 1-cells that would be most likely positioned at a radial distance of 150-200/~m (length of the dendrites). Axons of these interneurons are distributed in the space indicated by horizontal hatching and, therefore, have access to P-cell somata and dendrites located in the same zone. Inhibition surrounding the focus of excitation could be limited to this spheric shell if mediated purely by 1-ceU axons (option 2 in the text). Conversely, inhibition could also be effective in the entire solid zone of up to 400/tm in radius, i.e. the two stippled and the one hatched areas, if exercised through the 1-cell presynaptic dendrites (option 3 in the text). The left side of the diagram attempts to interpret the receptive field properties of the centrally located P-cell which can be considerred of the 'on-center, off-surround' type. A retinal afferent from the receptive field center (CENT AFF) would excite the P-cell. An afferent from the surround (SUR A F F A) would terminate on P-cells in the hatched zone and could result in inhibition of the central P-cell by way of the axon of the I-cell marked X which is located closer to the center. Another afferent from the surround (SURR A F F D) would terminate on P-cells in the outer stippled zone and could result in inhibition of the central P-cell through the dendritic tree of 1-cells located in the hatched area.

ful g e o m e t r y as t h a t f o u n d f o r e x a m p l e in t h e s p a t i a l a r r a y o f b a s k e t cells b o t h in t h e c e r e b e l l a r 6,27 a n d c e r e b r a l cortices29,31. G o l g i i m p r e g n a t i o n s are i d e a l l y suited to unravel such arrangements. Short local interneurons have been described with this m e t h o d in t h e t h a l a m i c a n d g e n i c u l a t e r e l a y n u c l e i in t h e e a r l y classic studies 14,23.

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These interneurons can be classified into two major groups. (1) The typical Golgi type I1 cell T M (labeled category III cell by Guilleryg), characterized chiefly by the presence of short drumstick-shaped dendritic appendages which increase in density, length and complexity towards the distal portions of the dendrites. Here they may branch and give rise to multilobed terminals as shown already in a photograph of SzentS, gothai e t al. a4 and more recently studied and illustrated in all relevant detail by Famiglietti and Peters s. There can be little doubt that these appendages are the presynaptic dendritic profiles present in the synaptic glomeruli and also outside of these structuresS,1a,15,17, as. (2) A 'neurogliform' or 'spidery' type cell mentioned already by Tello 3a and described and illustrated more recently by Pasik e t al. 17 These interneurons have numerous dendritic branches of characteristically beaded appearance. They seem to be rare in the cat, although they may be equivalent to the category V cell described by Famiglietti v. They are abundant in the L G N and M G N of the monkey. Since rather thin beaded dendrites showing presynaptic accumulations in the thickened parts are observed rather frequently in monkey material 17, it appears that presynaptic dendrites are common to both types of interneurons. The axons of all I-cells are below 1 # m in caliber and arborize within 50/zm from the soma. Their positive identification at the electron microscopy level would require a reconstruction of at least a portion of the process in question s, which is lacking at present. It is apparent that no specific geometric pattern describes the distribution of I-cell dendritic trees illustrated in the recent literature s,9,a4, or the terminal branching of optic fibers as. The following discussion is, therefore, based on a random geometry of arborizations considering that 1-cell dendrites are longer than the axon, and that the majority of synaptic articulations occur at the distal portions of the presynaptic dendrites 2s. Fig. 5 is a modified version of the model of Szent{tgothai 2s, which was originally proposed considering only classic neuronal components, i.e. without the knowledge o f presynaptic dendrites. The model depicts in simplified way the spatial relations of various actions occuring during transmission. The right half of the diagram shows only the theoretical areas of excitation and inhibition set up by a cluster of terminals from a retinal afferent making several contacts with the dendritic protrusions of a centrally located P-cell*. The interneurons receivi~lg many contacts from the same retinal afferent can be conceived as distributed in a spheric zone surrounding the focus of excitation. Since the distal ends of the interneuron dendrites have more numerous and profusely branching appendages than their proximal regions, it may be assumed that the most effectively stimulated I-cells in this case have their somata located in a spheric shell with a radius of about 200 #m, which is the approximate length of the dendrites. The axonal arborization of these interneurons, being within 50/zm distance from the cell body 17, would exercise inhibition in a zone of a sphere surrounding the focus of excitation between the radial distances of 150 and 250/zm, whereas inside and outside of that zone the axonal action

* The issue of how many retinal afferents contact one P-cell, and of how many P-cells are supplied by one afferent will be left open due to lack of sufficient information. Similar reservations apply to the ratio between P-cells and I-cells.

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would be negligible. Inhibitory actions of presynaptic dendrites would be effective in a solid zone from the focus to iadial distances of 250-400 #m. The left side o f the diagram offers three possible interpretations for the functions of 1-cells. (1) It may be assumed that the I-cell plays only a passive role by supporting the numerous dendritic appendages as small quasi interneurons. These quasi interneurons would be virtually independent from each other or interactions would occur only between neighboring appendages of the same dendrite. In such a situation, the function of the I-cell would be restricted to its participation in the triadic arrangement, and the axon, which undoubtedly exists, would be indeed superfluous. (2) Another option would consider the 1-cells as conventional inhibitory interneurons that, if receiving sufficient stimulation on their dendrites, would exercise inhibition through their axon in the hatched zone. Since I-cell axon terminals contact proximal dendrites, somata and even axon hillocks s of the P-cells, and since the vast majority of presynaptic contacts on 1-cells are established by specific afferents, this would be a classic case of forward (or parallel) inhibition. (3) A third option would assume that the I-cell dendritic tree might function as that of a true amacrine cell, i.e. upon receiving sufficient stimulation on one of its dendrites activation would propagate electrotonically (or perhaps even through conducted spikes) to the other dendrites resulting in the release of inhibitory mediator from the latter elements. The difficulty with this assumption is that it would have little use for the axons. It is obviously impossible to decide on these options on purely anatomical grounds. However, the distances illustrated in Fig. 5 for various types of actions might offer a clue. While a shell of inhibition at a radial distance of about 100-250 # m from the excited focus would favor an axonal mechanism (option 2) a larger inhibitory field extending from the center to a maximum of 400 # m would require a dendritic mechanism (option 3). In fact, option 3 does not rule out a coexistent axonally mediated action. Both mechanisms appear to be consistent with recent electrophysiologic findings of lateral inhibition in the L G N 25.

ACKNOWLEDGEMENTS

This research was supported in part by Grant No. MH-02261 from the National Institute of Mental Health, U.S. Public Health Service. The authors are indebted to Rosemary Lang, Nancy Gilbert, Lawrence Birkner and Victor Rodriguez for their skilful assistance.

REFERENCES 1 ANDERSEN,P., AND ECCLES, J. C., Inhibitory phasing of neuronal discharge, Nature (Lond.), 196 (1962) 645-647. 2 BOWSHER,D., Reticular projections to lateral geniculate in cat, Brain Research, 23 (1970) 247-249. 3 COLONNIER, M., AND GUILLERY, R. W., Synaptic organization in the lateral geniculate nucleus of the monkey, Z. Zellforsch., 62 (1964) 333-355.

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