The action of the corticofugal pathway on sensory thalamic nuclei: A hypothesis

0306-4522/87 $3.00 + 0.00 Pergamon Journals Ltd 6 1987 IBRO

Neuroscience Vol. 23, No. 2, pp. 399-406, 1987

Printed in Great Britain

COMMENTARY PATHWAY THE ACTION OF THE CORTICOFUGAL SENSORY THALAMIC NUCLEI: A HYPOTHESIS c. Divisions

ON

KOCH

of Biology and Engineering and Applied Science 216-76, California Institute of Technology, Pasadena, CA 91125, U.S.A.

Abstract-The N-methyl-D-aspartate receptor has recently attracted great interest due to its nonlinear current-voltage behavior. In order to evoke a large depolarizing postsynaptic current, the synapticinduced conductance change must be paired with a postsynaptic depolarization. This temporally tuned AND gate could underlie a number of different operations throu~out the nervous system. We propose that the synapses made by the optical nerve onto projection cells in the mammalian dorsal lateral geniculate nucleus are of the N-methyl-D-aspartate type. pn this Cozens, we have pooled data regarding sensory thalamic nuclei from a number of different mammalian species. Unless otherwise mentioned, we have referred to the dorsal division of the cat lateral geniculate nucleus.] About half of all synapses in these cells-located almost exclusively in the peripheral two-thirds of the dendritic tree-are associated with axons originating in layer VI of visual cortex. It then follows that the massive corticogeniculate pathway controls the gain of the retinogeniculate pathway via its action on the N-methyl-o-aspartate receptors. Thus, near-simultaneous activation of the retinal and the cortical input will transiently enhance the geniculate cell response. Generalizing to other thalamic sensory nuclei, afferent information will be routed through the thalamus and on to the cortex as long as cortical activity is congruent with sensory input to the thalamus. Experimental evidence argues for a such a mechanism to control the gain of the somatosensory input to the ventrobasal thalamic nucleus.

CONTENTS 1. INTRODUCTION

399

2. N-METHYL-D-ASPARTATE 3. MAMMALIAN 4. CORTICAL

RECEPTORS

399

LATERAL GENICULATE

NUCLEUS

INPUT

400 401

5. A NEW PROPOSAL

402

6. EVIDENCE AND PREDICTIONS

402

7. DISCUSSION

403

ACKNOWLEDGEMENTS

404

REFERENCES

404

1. INTRODUCTION One of the most puzzling riddles in neurophysiology is the function of the massive projection from the cortex back to the thalamus. Within the visual system, layer VI of visual cortex feeds back to the lateral geniculate nucIeus (LGN), a projection which surpasses the forward projection from the LGN to visual cortex in total number of fibers. However, removing or jnactivat~n~ visual cortex only leads to minor changes in cellular excitability in the LGN. Moreover, the receptive fields of genicuiate neurons differ

only a little from their retinal counterparts. Thus, since both the action and the function of this corticofugal pathway remain an enigma, it is widely held that the LGN serves solely as a relay station between the retina and the visual cortex, with littk intrinsic processing power. In contrast, it has recently been proposed that the highly intricate geniculate circuitry, in conjunction with its complex electrophysiological make-up, underlies state-specific gating of visual info~ation.i~.6z.~3

A very large number of neurons found in the brain EPSP, excitatory postsynaptic potential, LGN, lateral g&&ate use the amino acid glutamate as their neuronucleus; NMDA, N-metbyl-a-aspartate. transmitter, producing a short depolarizing response

Abbreviations: APV, amino-phosphonovalerate;

399

400

C.

in their postsynaptic target. Glutamate receptors come in several flavors, classified according to the different agonists they are sensitive to. Thus, at least three different glutamate receptors can be distinguished, according to whether they are excited by kainate, quisqualate, or N-methyl-n-aspartate (NMDA). 20.49In the past, the relevance and function of NMDA receptors has been controversial, since they do not seem to mediate conventional fast excitation; blockage of NMDA receptors via a specific blocker of these receptors, amino-phosphonovalerate (APV), has little effect on excitatory synaptic transmission. A number of recent biophysical studies have thrown light on the behavior and function of NMDA receptors in the mammalian nervous system.‘4,34,50,‘3 If neurotransmitter binds to a receptor, its molecular configuration changes, inducing a change in the conductance of the postsynaptic membrane. At the neuromu~ular junction, for instance, the conductance for sodium increases and an excitatory postsynaptic potential (EPSP) is generated. One major feature distinguishing NMDA receptors from his siblings is that the increase in membrane conductance upon binding of NMDA to the receptor depends on the postsynaptic potential. If the cell is at its resting potential (approximately - 75 mV) or hyperpolarized, direct application of NMDA has only very little effect. Above resting potential, and up to about -35 mV, the inward, excitatory current induced by a given dose of NMDA increases with increasing depolarization of the cell. Explanations of this behavior have revolved around the idea that the NMDA receptor is coupled to a voltage-sensitive conductance, similar to the voltage-dependent channels underlying action potentials.‘s.18 Recent experiments have revealed a different story:50.53if magnesium is removed from the extracellular environment, the NMDA receptor shows the voltage independency expected from a number of his class. At physiological concentrations of extracellular magnesium {in the low millimolar range), however, Mg2+ physically blocks the channel at negative potentials. If the ceil is more depolarized, the magnesium ions are driven out of the channel and a ~isch~g of sodium and calcium ions enters the cell,‘5,45generating an EPSP. This phenomenon explains the negative conductance region seen in the receptor’s current-voltage relationship (Fig. 1). The unique dependency of the NMDA receptor on both neurotransmitter and postsynaptic potential makes it an attractive candidate for implementing synaptic operations of the AND type; only the simultaneous presence of a presynaptic input to the NMDA receptor in conjunction with a second depolarizing synaptic input assures the generation of a strong EPSP. In particular, if both inputs are spatially restricted to subunits of the dendritic tree, a number of very local operations can be synthesized, similar to the AND-NOT type of synaptic logic proposed by Koch et ~f.~‘.~’ on the basis of the

KOCH

+3 HoA)

1

i

‘c/l V(m -2 J

Fig. 1. Current-voltage relationship of the NMDA receptor recorded in cultured mouse spinal cord neurons. The negative slope of the graph between - 35 and -75 mV, indicating voltage sensitivity of the NMDA response, is the region where our proposed AND mechanism operates. Redrawn from Mayer et al.%

nonlinear interaction between excitation and silent or shunting inhibi~on. Recent interest in NMDA receptors concerns their possible role in inducing associative long-term potentiation in CA1 hippocampal slice neurons,8*~29 3. MAMMALIAN

LATERAL

GENICULATE

NUCLEUS

Cells in the dorsal Iateral geniculate nucleus can be subdivided into at least two morphologically distinct cell classes: relay cells and interneurons (for reviews see Refs 36 and 61). In the cat, about 7&80% of all cells in the A and AI layers are relay cells, i.e. they project to layer IV and to a lesser extent to layer VI of striate cortex (area 17). In addition a subpopulation of relay cells (Y cells) projects to extrastriate cortex (areas 18, 19 and lateral suprasylvian cortex). Perhaps 20-30% of cells in the LGN contain the inhibitory amino acid GABA and are believed not to project to the cortex. “,j4 In the primate LGN, similar numbers appear to hold. One major species difference is that in monkey the projection is weak to extrastriate areas.9g70Relay cells receive all of their retinal input from one or very few retinal ganglion cells of the same type (on or off, X or Y, parvo or magno). Thus, the receptive field of each geniculate cell is very similar to that of its retinal input.‘0,3’*60,M Cells in the LGN receive only monocular retinal input; in other words, the LGN can be considered an internal “copy” of both retinae. In spite of the fact that geniculate cells appear to be exclusively driven by retinal input, only a minority of synapses originate in the retina. Four major synaptic profiles have been identified in the LGN, accounting for at least 95% of all synaptic

401

Action of the corticofugal pathway

Retinal fibers contribute IO-20% of as Galago, there is an acetylcholinesterase-rich profiles. 2i~24~25*27~08 projection feeding back from the striate cortex to the all synapses while terminals from corticofugal fibers parvocellular layers of the LGN that is not present in account for 4Q-45% of all synapses in the LGN. Fl terminals derive from axons originating mainly in the diurnal primates such as Mucuca (for an overview of reticular nucleus of the thalamus (and to a lesser this striking correlation see Ref. 4). On their way to the thalamus, all corticofugal extent from axons of local cells in the geniculate”?. fibers pass through a sheet-like structure, termed F2 terminals derive from the dendrites of geniculate reticular nucleus of the thalamus, enveloping much of intemeurons.17~27~28Both Fl and F2 synapses have the dorsal thalamus (see Fig. 2).3s.58 The perineurosymmetric profiles, use the inhibitory transmitter GABA and account for about 40% of all geniculate nucleus is usually considered to be the visual part of the reticular nucleus,“.63 although some synapses. consider it to be a separate thalamic nucleus.2 It is The synaptic input to neurons in the LGN is not believed that most, if not all, of the axons passing distributed homogeneously over the available memto and from cortex through this structure make brane area. Instead, it has been consistently observed excitatory contacts there.3~‘6~21~33 As noted above, that the retinal input terminates on the proximal third of the dendritic tree of geniculate relay cell~.*~~*~*~* In neurons in the thalamic reticular nucleus are GABAergic and, thus, inhibitory.sz,~,63 cat, relay cells receive the majority of their 20@400 retinal terminals onto either dendritic appendages or spines (in X cells) or the dendritic stem (in Y cells), within lOOhm from the soma.48*68Both Fl and F2 Visual terminals contribute a sizeable fraction (lO-20%) to Cortex the total synaptic count on distal dendrites of relay cells, where no retinal inputs are observed. Terminals from co~icofugal fibers are always in direct contact with the dendritic stem and rapidly become the predominant synaptic input only a few tens of micrometers from the soma of relay cells.21~24,27*28~37 In fact, beyond 1OOpm almost no retinal input is observed. Geniculate interneurons receive contacts from both cortical and Fl te~inals (as well as retina1 input) throughout their dendritic tree.28 In summary, the two major afferent pathways feeding into the LGN are spatially segregated: retinal input is localized to the proximal third and cortical input to the distal two-thirds of the dendritic tree. 8

TTT

4. CORTICAL INPUT The cortical projection to the LGN originates among layer VI pyramidal cells in areas 17, 18 and 19 in the cat,24-37while it is confined to area 17 in the primate.* In the cat, about half of all layer VI pyramidal cells contribute to the ~~icogeniculate pathway.23 It has been estimated that each geniculate relay cell receives convergent input from at least 10

cortical cells and most likely much more.62 The corticogeniculate axons monosynaptically excite their target c=ells-both relay cells and interneurons-in a topographic manner. ‘3%The latencies of the cortically induced EPSPs are between 2 and 5 ms, with some showing latencies up to 13-18 rns.‘nMThese relatively long delays are in agreement with the fact that only the very thinnest myelinated fibers degenerate after cortex lesions.37 There is evidence implicating glutamate as the neurotransmitter of corticofugal cells.7*8*‘9 Interestingly, in night-active primates such *There appears to he a sparse anatomical projection from area 18 and the middle temporal area (MT) onto the LGN in the owl monkey.M

I

I

’

I

1

Retina

I

I

I I

Fig. 2. Highly schematic diagram illustrating the afferent and efferent projection to and from the mammalian lateral geniculate nucleus (LGN). Full arrowheads indicate fast, excitatory connections, while open arrows stand for more complex postsynaptic actions. The feedback from visual cortex to the LGN (thin lines) is numerically far stronger than the forward projection. This pathway innervates, on its way to the LGN, neurons in the reticular nucleus of the thalamus (NRT), .which is frequently identified with the perigeniculate nucleus (see, however, Ref. 2). These GABAergic neurons in turn project back onto geniculate interneurons and projection cells. in cat, a fraction of geniculate projection cells make synapses in the NRT on their way to cortex. The midbrain* reticular formation (MRF) pathway to both the thafamus and the cortex consists of a number of separate pathways with different postsynaptic actions and time-courses. It includes at least cholinergic, noradrenergic and serotonergic fibers. Other sensory thalamic nuclei have a similar circuit diagram.

402

C.

At the moment, the exact nature of the mapping between layer VI of cortex, the reticular nucleus and the LGN is not known. If cells in all three structures are in complete spatial register, an activated corticofugal cell would induce an EPSP in its geniculate target cell, followed I-2ms later by an inhibitory postsynaptic potential. However, it is likely that in spite of the topographic nature of the feedback, the connections between the reticular nucleus and the LGN are slightly offset:62 activation of a corticofugal cell excites its geniculate target cells while inhibiting certain of its neighbors, consistent with crosscorrelation studies,” revealing an excitatory pathway between corticogeniculate and geniculate cells if the receptive field center of both neurons are separated by less than 1.I degrees. Larger separations produce inhibitory interactions. Given the highly visible anatomical presence of corticofugal fibers in the geniculate nucleus, a number of studies have tried to address the question of its function by reversibly inactivating cortical input. The observed effects are contradictory and never dramatic. After cooling cortex, Schmieiau and Singers9 report a significant decrease in geniculate activity (see also Ref. 1). Kalil and Chase3’ some decrease, Richard et ~1.~~ no significant effect, Baker and Malpel? (as well as Marrocco ez ~1.~~using a different technique) an increase in activity, while Hull32 and Geisert et al.** have seen complex, mixed effects with both excitatory and inhibitory actions. How can these conflicting reports be explained? It has been argued that the corticofugal feedback underlies attention-like phenomena”.62.6’ Thus, since most of these experiments have been carried out on anesthetized animals, it is not very surprising that no loss of attention-related behavior has been reported, since such a behavior will not be expressed in an anesthetized animal. A second explanation is based on the corticogeniculate circuitry (see Fig. 2). Removing cortical input by inactivating all cells in layer VI removes one direct source of excitation to geniculate cells. But this procedure also removes two indirect sources of inhibition (via GABAergic interneurons in both the reticular nucleus and the gcniculate) and one indirect source of disinhibition (via GABAergic neurons in the reticular nucleus inhibiting GABAergic interneurons in the geniculate inhibiting geniculate relay cells). Third, in most experiments geniculate cell excitability was tested in response to flashing lights and bars before and after cooling visual cortex (see, however, Ref. 67). Such conventional receptive field stimuli may only weakly drive corticogeniculate cells, thereby making an effective assessment of their function difficult. 5. A

NEW PROPOSAL>

Our central hypothesis is: a fraction of the retinogeniculate synapses are of the NMDA type. From this, it follows that: the corticogeniculate input con-

KOCH

trols the effectiveness or gain of the retinogeniculate synapses. The EPSP caused by the cortical input on distal dendrites depolarizes more proximal dendrites, causing Mg*+ to move out of the pore of the NMDA receptor. Due to the nonlinearities inherent in the NMDA receptor (Fig. I), the retinal input will now induce a much larger EPSP than in the absence of the cortical input. Due to the spatial segregation of synaptic input to relay cells, individual cortical afferents could-in principle--control the contribution of individual retinal cells toward geniculate cell excitability. This notion presupposes that at least some retinal and cortical afferents selectively innervate and limit their synapses to parts of the dendritic tree of geniculate relay cells. The proposed function of the cortical input is not to depolarize the soma, thereby bringing the cell closer to threshold, but instead to boost and control the gain of the retinogeniculate synapse. Due to the location of the retinal input, intermediate between the soma and the cortical input, a cortical induced EPSP might double the postsynaptic current flowing through the NMDA receptor by depolarizing the dendrite from -70 to -50 mV (see Fig. 3c in Ref. 50), while contributing much less than 20mV to the somatic potential. The degree of enhancement depends on the temporal overlap between the cortical induced EPSP and the conductance change at the NMDA receptor. This modulatory role of the cortical input explains why little change in spontaneous geniculate cell activity is seen following cooling of cortex. Note that in order to prevent retinal input by itself to switch the NMDA receptor into its more conducting state, we have to assume that the retinal EPSP is insufficient by itself to induce Mg’ ’ to move out of the channel. Additional excitatory input, e.g. cortical input, must be required to elevate the membrane potential to sufficiently high levels. 6.

EVIDENCE AND PREDICTIONS

Experimental evidence for our proposal comes mainly from the ventrobasal thalamic nucleus, that is, the part of the thalamus involved in transmitting somatosensory information to cortex. Kemp and Sillito4’ studied the nature of the excitatory transmitter mediating retinal input to cat geniculate relay cells. Using pharmacological antagonists, they argue that either aspartate or glutamate serves as neurotransmitter, specifically favoring the involvement of NMDA receptors. A study of Salt5’ goes even further, showing that NMDA receptors play a crucial role in mediating sensory input to the ventrobasal part of the rat thalamus. Cells in the ventrobasal thalamus were excited by either physiological (using small puffs Of air) or artificial stimuiation {by electrical stimulation of the somatosensory afferents), and the specific NMDA receptor blocker APV was applied. Surprisingly, APV completely blocks the response of the thalamic cells to the physiological stimulus while it

403

Action of the corticofugal pathway has little effect on the short-latency excitation seen upon electrical stimulation. The response to electrical stimulation could be blocked, however, if it was repeated at a 20 Hz frequency. This experiment indicates that in at least one thalamic nucleus, afferent input is partly mediated by NMDA receptors. Yuan et al.@ investigated the function of the corticofugal fibers in ventrobasal thalamic neurons of the awake, non-anesthetized rat. Using both electrical stimulation of the medial lemniscus or stimulation of the receptive field of the thalamic cells as test probes, the response of these cells before and after suppression of the somatosensory cortex (using magnesium or lidocaine) was measured. The majority of neurons react to the silencing of cortex by a clear reduction in the number of evoked spikes per stimulation event. This reduction is greatest during a stimulation frequency of l&30 Hz. The results of Yuan et al. can clearly be explained within the framework espoused above. Recently, Valera and Singe8” revealed one property of the corticogeniculate pathway in the anesthetized cat. They recorded from a given geniculate cell, using as stimulus a grating shown to the (dominant) eye exciting the geniculate relay cell. Subsequently, they studied its response in the presence of a second grating of different orientation presented to the nondominant eye. Although the geniculate cell receives no direct input from this eye, its response decreases; this long-latency inhibition increases in general with increasing mismatch between the gratings presented to the two eyes. Ablation of visual cortex abolished the inhibition. Our mechanism provides a simple explanation for Valera and Singer’s results: increasing mismatch between inputs to the two eyes leads to a mismatch between retinal and cortical input to LGN relay cells; thus, due to the properties of the retinal NMDA receptors, this mismatch will functionally act like inhibition, since it will decrease the effectiveness of the retinogeniculate synapse. One recent study of retinal input to the LGN is at odds with our hypothesis. Crunelli et af.‘*-13studied the nature of the excitatory amino acid used at the optic nerve receptors in the dorsal and ventral LGN of the rat in uitro. While gamma-o-glutamylglycine, an excitatory amino antagonist, reversibly inhibited the postsynaptic response evoked in geniculate cells upon electrical stimulation of the optic tract, the highly specific NMDA antagonist APV had no such effect, leading Crunelli et al. to conclude that the transmitter of the optic nerve is a glutamate-like substance, but that NMDA receptors are not directly involved in the transmission. When interpreting these results two points must be taken into account. First, Salt” specifically showed that the response of ventrobasal rat neurons could be blocked by APV when the somatosensory afferents were excited by natural stimulation but that the short-latency response seen upon electrical stimulation of the afferents could not be blocked. Second, the rat dorsal LGN is thought to

correspond to the parvocellular C layers in the cat dorsal LGNz6s4’on the basis of synaptic organization and origin of non-retinal input (e.g. from superior colliculus). Since the majority of cat retinal X and Y cells project onto the prominent A layers which also receive the strongest corticogeniculate feedback,6’ the experiments of Salt5’ and Crunelli et al.‘2-‘3 should properly be repeated in these layers. That is, the response of these cells to visual stimuli should be recorded during application of APV or some other NMDA antagonist. Also, the non-classical behavior of the NMDA receptor (see Fig. 1) distinguishes it from the non-NMDA type receptors and could be studied using intracellular recordings. Finally, due to the segregation of retinal and cortical input, immunocytochemical or autoimmunoradiographical assays for NMDA receptors at the electron-microscopic level should reveal heavy staining in the proximal third and a much-reduced staining density in the periphery of relay cell dendrites. 7. DISCUSSION

At the moment, we can only guess as to the function of the corticogeniculate feedback. Depending on the kinetics of the NMDA receptor and on the extent of temporal overlap between the retinal induced conductance change and the cortical induced EPSP, this receptor acts as a temporally tuned AND gate, selecting only those retinal inputs arriving coincident with, or within 5--20ms following, cortical input. Given the LGN-cortex-LGN loop, such a facilitation could result in wave-like repetitive firing activity at the level of the LGN, with its carrier frequency being determined by the delay between layer IV afferent and layer VI efferent activity. Thus, generalizing to other thalamic nuclei, the corticothalamic pathway could provide a fast and topographic pathway to control selectively the gain of the sensory input to thalamic cells. This contrasts with the ascending projections from the mesencephalic reticular formation to the thalamus (among others, the noradrenergic projection from the locus coeruleus, the cholinergic projection from the parabrachial nucleus, and the serotonergic projection from the dorsal raphe nucleus), which act over longer temporal time scales (at least 100 ms) and on a much coarser spatial resolution (for more details, consult Ref. 62). But what is the function of the cortical feedback to the geniculate in particular, and to the thalamic sensory nuclei in general? We cannot but feel that it is involved in selectively and transiently enhancing conspicuous or otherwise interesting features in sensory-stimulus space. In other words, higher cortical areas detect the presence of significant featuresfor instance, a red blob surrounded by green blobs or a small moving patch on a stationary backgroundand relay this information back to the corresponding location in the geniculate. Due to the conjunction of

404

c. KOCH

retinal and corticogeniculate input, the response of the geniculate cells will be enhanced, making the corresponding location stand out for selective visual attention to lock onto it (for more details see Ref. 43). In the more radical version of this theory, the entire input to striate cortex from the thalamus would be limited to those locations where retinal and corticothalamic inputs coincide. In principle, this could be one or very few patches which shift-via appropriate shifts in the excitability of the corticogeniculate cells-throughout the visual scene, const~cting a detailed rep~sentation of the visual environment via a small number of serial processes. These ideas are related to the proposal by Crick” that the pathway from the reticular nucleus of the thalamus controls the expression of the attentional searchlight proposed by Julesz, 38 Treisman6s and others on the basis of psychophysi~l evidence. We would like to advance a second proposal. If cortical activity is congruent with afferent sensory input to the thalamus, the afferent information will be routed through the thalamus and on the cortex. Thus, the corticothalamic pathway could act as a predictor to test for the presence of certain stimuli. For instance, if some cortical area (e.g. middle temporal or medial superior temporal area in primates) extrapolates from the current movement of an object its position some time into the future, it could excite the appropriate layer VI cell which in turn facilitates the retinal input if the retinal input arrives within the appropriate time-window defined by the overlap between the NMDA-induced conductance change and the geniculate postsynaptic response. Thus, cortex could predict the two- or even the three-dimensional position of moving objects and evaluate the correctness of these predictions by monitoring the geniculate output. Such predictions could occur throughout the entire visual field in a parallel fashion and would explain the massive nature of the feedback, since specifying movement in different directions or

binocular disparity at each location in the visual field requires a very large number of independent control lines (this idea is somewhat related to the dynamic shifter proposal by Anderson and Van Essen’). Two alternative sets of ideas are those of Harth et ~1.~’who propose the use of brainstem and cortical feedback to optimize perception, and of Singer.‘j” Singer proposed that the corticogeniculate feedback selectively facilitates the transmission of signals from binocularly viewed objects near the fixation plane, thereby facilitating fusion of the images from the two eyes. This intriguing proposal does not explain, however, why the corticogeniculate feedback exists in the monocular part of the cat LGN, nor does it offer any rationale for the existence of the feedback in animals with no, or very little, binocular overlap, or in the non-visual parts of the thalamus. At the moment, it appears that the stumbling block towards a theory of the corticothalamic feedback is the lack of unambiguous experimental support showing modification of retinocortical transmission during activation of the corticothalamic pathway. Two different categories of experiments are needed. An ideal biophysical experiment would combine precise pharmacologicai tools to block the different afferent pathways to thalamic sensory nuclei with simultaneous recording/stimulation electrodes in layer VI of cortex and in the thalamus to explore the role of the feedback at the single cell level. A more behaviorally oriented experiment would assess the performance of monkeys under some “attentional” paradigm before, during, and after temporary inactivation of corticothalamic synapses (most likely via some pharmacological agent).

Acknowledgements-I thank Drs Francis Crick, Murray Sherman and David Van Essen for always lending a recep tive ear to my speculations. This research was supported by

the Charles Lee Powell Foundation and the Boeing Faculty Development Fund.

REFERENCES

I. Ahlsen G., Grant K. and Lindstrom S. (1982) Monosynaptic excitation of principal cells in the lateral geniculate nucleus

by corticofugal fibers. Bruin Res. 234, 454-458. 2. Ahlsen G., Lindstrijm S. and Lo F.-S. (1982) Functional distinction of perigeniculate and thalamic reticular neurons in the cat. Expl Brain Rex 46, 118-126. 3. Ahlsen G. and Lindstrom S. (1982) Excitation of perigeniculate neurones via axon collaterals of principal cells. Brain Res. 236, 477-48 1. 4. Allman J. and McGuinness E. (In press) Visual cortex in primates. In Comparative Primate Biology (ed. Stehlis H.). 5. Anderson C. H. and Van Essen D. C. (In press) Shifter circuits: a computational strategy for dynamic aspects of visual processing. Proc. natn. Acad. Sci. U.S.A. 6. Baker F. H. and Malpeli J. G. (1977) Effects of cryogenic blockade of visual cortex on the responses of lateral geniculate neurons in the monkey. Expl Brain Res. 29, 433-444. 7. Baughman R. W. and Gilbert C. D. (1981) Aspartate and glutamate as possible neurotransmitters in the visual cortex. f. N;?rrosci. 1, 427-439. 8. Bromberg M. D., Panney J. B., Stephenscon B. S. and Young A. B. (1981) Evidence for glutamate as the neurotransmitter of corticothalamic and corticorubial pathways. Bruin Res. 214, 369-374. 8a. Brown T. H.. Ganong A., Kelso S. and Keenan C. L. (In press) Associative ATP. In Nearal Models of Plasticity (eds Berry W: 0. and-Byrne J. H.). Academic Press, New York. 9. Bullier J. and Kennedv H. (1983) Projection of the lateral geniculate nucleus onto cortical area V2 in the macaque monkey. Expl Brain Rfes. 5j, 168-172:

Action of the corticofugal pathway

405

10. Cleland B. G,, Dubin M. W. and Lerick W. R. (1971) Sustained and transient neurons in the cat’s retina and lateral geniculate nucleus. J. Physiol., Land. 217, 473-496. 11. Crick F. (1984) Function of the thalamic reticular complex: The searchlight hypothesis. Proc. nufn. Acad. Sci. U.S.A. 81, 4586-4590: 12. Crunelli V., Kelly J. S., Leresche N. and Pirchio M. (1987) The ventral and dorsal lateral geniculate nucleus of the rat: cellular recordings in vitro. J. Physiool., Land. 384, 587-601. 13. Crunelh V., Kelly J. S., Leresche N. and Pirchio M. (1987) On the excitatory postsynaptic potentiai evoked by stimulation of the optic tract in the rat lateral geniculate nucleus. J. Physiof., Land. 384, 603-618. 14. Cull-Candy S. G. and Usowicz M. M. (1987) Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nuture 325, 525-528. activates voltage-dependent calcium conductance in rat hippocampal 15. Dingledine R. (1983) N-Methyl-n-aspartate pyramidal cells. J. Physiol., Land. 343, 385-405. 16. Dubin M. W. and Cleiand B. G. (1977) Org~i~tion of visual inputs to interneurons of lateral geniculate nucleus of the cat. J. Neurophysiol. 40, 410-427. 17. Fitzpatrick D., Penny G. R. and Schmechel D. E. (1984) Glutamic acid d~rboxyla~-immunoreactive neurons and terminals in the lateral rreniculate nucleus of the cat. J. Neurosci. 4, 1809-1829. 18. Flatman J. A., Schwind; P. C., Grill W. E. and Stafstrom C. E. (1983) Multiple actions of N-methyl-o-aspartate on cat neocortical neurons in vitro. Brain Res. 266, 169-173. 19. Fonnum F.. Storm-Mathisen J. and Divac I. (1981) Biochemical evidence for glutamic neurotransmitter in corticostriatal and corticothalamic fibers in rat brain. Nehroscienee 6, 863-873. 20. Foster A. C. and Fagg G. E. (1984) Acidic amino acid binding sites in mammalian neuronal membranes: Their characteristics and relationship to synaptic receptors. Bruin Res. Rev. 7, 103-164. 21. Friedlander M. J., Lin C.-S., Stanford L. R. and Sherman S. M. (1981) Morphology of functionally identified neurons in the lateral geniculate nucleus of the cat. J. Neurophysiol. 46, 8G129. 22. Geisert E. E., Langsetmo A. and Spear P. D. (1981) Influence of the corticogeniculate pathway on response properties of cat lateral geniculate neurons. Brain Res. 2@8, 409415. 23. Gilbert C. D. and Kelly J. P, (1975) The projections of cells in different layers of the cat’s visual cortex. J. camp. Neural. 163, 81-106. 24. Guillery R. W. (1967) Patterns of fiber degeneration in the dorsal lateral geniculate nucleus of the cat follo~ng lesions in the visual cortex. J. camp. Neural. 130, 197-222. 25. Guillery R. W. (1971) Patterns of synaptic interconnections in the dorsal lateral geniculate nucleus of the cat and monkey: a brief review. Vision Res. Suppl. 3, 21 l-227. 26. Hale P. T., Sefton A. J. and Dreher B. (1979) A correlation of receptive field properties with conduction velocity of cells in the rat’s retino-geniculo-cortical pathway. Expf Brain Rex 35, 425-442. 27. Hamos J. E,, Van Horn S. C., Raczkowski D. and Sherman S. M. (1987) Synaptic circuits involving an individual retinogeniculate axon in the cat. J. camp. Neural. 259, 165192. 28. Hamos J. E., Van Horn S. C., Raczkowski D., Uhlrich D. J. and Sherman S. M. (1985) Synaptic ~onnecti~ty of a local circuit neuron in the cat’s lateral geniculate nucleus. Nurure 317, 618621. 29. Harris E. W., Ganong A. H. and Cotman C. W. (1984) Long-term potentiation in the hippocampus involves activation of N-methyl-u-aspartate receptors. Brain Res. 323, 132-137. 30. Harth E., Unnikrishnan K. P. and Pandya A. S. (1987) The inversion of sensory processing by feedback pathways: a model of visual cognitive functions. Science, N.Y. 237, 184-187. 31. H&e1 D. II. and Wiesel T. N. (1961) Integrative action in the cat’s lateral geniculate body. J. Physioi., Lond. 155, 385-398. 32. Hull E. M. (1968) Corticofugal influence in the macaque lateral genicnlate nucleus. Vision Res. 8, 128S-1297. 33. Ide L. S. (1982) The fine structure of the nerineniculate nucleus in the cat. J. coma. Neuroi. 210. 3l7-334. 34. Jahr C. E.‘and Stevens C. F. (1987) Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325, 522-525. 35. Jones E. G. (1975) Some asoects of the organization of the thalamic reticular comolex. J. coma. 1 Neural. 162.285308. 36. Jones E. G. (1985) The Th&tnus. Plenum Press, New York. 37. Jones E. G. and Powell T. P. S. (1969) An electron microscopic study of the mode of termination of cortico-thalamic fibres within the sensory relay nuclei of the thalamus. Proc. R. Sot. B172, 173185. 38. Julesx B. (1984) A brief outline of the texton theory of human vision. Trends Neurosci. 7, 41-45. 39. Kalil R. E. and Chase R. (1970) Corticofugal influence on activity of lateral geniculate neurons in the cat. J. Neurophysiol. 33, 459-474.

40 Kemp J. A. and Sillito A. M. (1982) The nature of the excitatory transmitter mediating X and Y cell inputs to the cat dorsal lateral geniculate nucleus. J. Physiol., Lond. 323, 377-391. 41. Koch C., Poggio T. and Torre V. (1982) Retinal ganglion cells: a functional interpretation of dendritic morphology. Phif. Trans. R. Sot. B298, 227-264. 42. Koch C., Poggio T. and Torre V. (1986) Computations in the vertebrate retina: gain enhancement, differentiation and motion discrimination. Tren& Neurosci. 9, 204-211. 43. Koch C. and Ullman S. (1985) Shifts in selective visual attention: towards the underlying neural circuitry. Human Neurobiol. 4, 219-227.

44. Liu C. S. and Kass J. H. (1976) Projections from cortical visual areas 17, 18 and MT onto the dorsal lateral geniculate nucleus in owl monkeys. J. camp. Neural. 173, 457-474. 45. MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J. and Barker J. L. (1986) NMDA-receptor activation increases cytoplasmic cakium ~n~ntration in cultured spinal cord neurons. Nature 321, 51952I. 46. Marroao R. T., McClurkin J. W. and Young R. A. (1982) Modulation of lateral geniculate nucleus cell responsiveness by visual activation of the corticogeniculate pathway. J. Neurosci. 2, 256263. 47. Martin P. R. (1986) The projection of different retinal ganglion cell classes in the dorsal lateral geniculate nucleus in the hooded rat. Expl Brain Res. 62, 77-88. 48. Mason C. A., Guillery R. W. and Rosner M. C. (1984) Patterns of synaptic contract upon individually labeled large cells of the dorsal lateral geniculate nucleus of the cat. Neuroscience 11, 319-329.

406

C.

KOCH

49. Mayer M. L. and Westbrook G. L. (1984) Mixed-agonist action of excitatory amino acids on mouse spinal cord neurons under voltage clamp. .I. Physiol., Lond. 354, 29-53. 50. Mayer M. L., Westbrook G. L. and Guthrie P. B. (1984) Voltage dependent block by Mg*+ of NMDA responses in spinal cord neurones. Nature 309, 261-263. 51. Montero V. M. and Scott G. L. (1981) Synaptic terminals in the dorsal lateral geniculate nucleus from neurons of the thalamic reticular nucleus: a light and electron microscopic autoradiographic study. Neuroscience 6, 2561 2577. 52. Montero V. H. and Singer W. (1984) Ultrastructure and synaptic relations of neural elements containing glutamic acid decarboxylase (GAD) in the perigeniculate nucleus of the cat. Expl Brain Res. 56, 115-125. 53. Nowak L., Bregestovski P., Ascher P., Herbert A. and Porchiantz A. (1984) Magnesium gates glutamate-activated channels in mouse central neurons. Nature 307, 4633465. 54. O’Hara P. T., Sefton A. J. and Lieberman A. R. (1980) Mode of termination of afferents from the thalamic reticular nucleus in the dorsal lateral geniculate nucleus of the rat. Brain Res. 197, 5033506. 55. Richard D., Gioanni Y., Kitsikis A. and Buser P. (1975) A study of geniculate unit activity during cryogenic blockade of the primary visual cortex in the cat. Expl Brain Res. 22, 2355242. 56. Robson J. A. (1983) The morphology of corticofugal axons to the dorsal lateral geniculate nucleus in the cat. J. cotnp. Neural. 216, 89-103. 57. Salt T. E. (1986) Mediation of thalamic sensory input by both NMDA receptors and non-NMDA receptors. Nature 322, 263-265. 58. Scheibel M. E. and Scheibel A. B. (1966) The organization Brain Res. 1, 43-62.

of the nucleus of the reticularis thalami: a Golgi study.

59. Schmielau F. and Singer W. (1977) The role of visual cortex for binocular interactions in the cat lateral geniculate nucleus. Brain Res. 120, 354361. 60. Shapley R. and Lennie P. (1985) Spatial frequency analysis in the visual system. A. Rea. Neurosci. 8, 5477583. 61. Sherman S. M. (1985) Functional organization of the W-, X- and Y-cell pathways: a review and hypothesis. In Progress in Psychobiology and Physiological Psychology (eds Sprague J. M. and Epstein A. N.), Vol. 11, pp. 23333 14. Academic Press, New York. 62. Sherman S. M. and Koch C. (1986) The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus. Expl Brain Res. 63, l-20. 63. Singer W. (1977) Control of thalamic transmission by corticofugal and ascending reticular pathways in the visual system. Physiol. Rev. 57, 386420. 64. Singer W. and Creutzfeldt 0. D. (1970) Reciprocal lateral inhibition of On- and Off-Center neurones in the lateral geniculate body of the cat. Expi Brain Res. 10, 311-330. 65. Treisman A. (1986) Features and objects in visual processing. Cent. Am. 255, 106115. 66. Tsumoto T., Creutzfeldt 0. D. and Legendy C. R. (1978) Functional organization of the corticofugal system from visual cortex to lateral geniculate nucleus in the cat. Expl Brain Res. 32, 345-364. 67. Varela F. J. and Singer W. (1987) Neuronal dynamics in the visual corticothalamic pathway revealed through binocular rivalry. Expl Brain Res. 66, l&20. 68. Wilson J. R., Friedlander M. J. and Sherman S. M. (1984) Ultrastructural morphology of identified X- and Y-cells in the cat’s lateral geniculate nucleus. Proc. R. Sot. B221, 411436. 69. Yuan B., Morrow T. J. and Casey K. L. (1986) Corticofugal influences of Sl cortex on ventrobasal thalamic neurons in the awake rat. J. Neurosci. 8, 3611-3617. 70. Yukie M. and Iwai E. (1981) Direct projection from the dorsal lateral geniculate nucleus to the prestriate cortex in macaque monkeys. J. comp. Neural. 201, 81-97. (Accepted 22 June 1987)