Monocular inhibition in the lateral geniculate body

M O N O C U L A R INHIBITION IN THE LATERAL G E N I C U L A T E BODY

E. F. VA~OLA, M . D . Division of Neurology, State University of N. Y., Co//ege of Medicine, Brooklyn 3, N.Y.

(Received for publication: June 22, 1959) INTRODUCTION

conditioning and test stimulation were apThe post~synaptie spike response of neu- plied to the same optic nerve. Observations rons in the dorsal nucleus of the lateral geni- made under these conditions are relevant to culate body (LGD) to electrical stimulation the general problem of interaction between of the optic nerve is followed by prominent parallel elements in the visual system. More after-positivity (fig. 1 and 2, B) which has specifically, an attempt was made to answer been shown to signal inhibition of principal the following question: To what extent does (radiation axon) cells as measured by their inhibition which accompanies after-positivity ability to produce an action spike when chal- elicited by activity in a given group of optic lenged by either an orthodromic or antidromic nerve fibers act upon principal cells instimulus (Vastola 1959). After-positivity has nervated by some smaller portion of the same consequently been attributed to hyper-polar- group of optic fibers ? The elegant investigaization of the cell bodies, and perhaps portions tions with micro-electrodes performed by of the dendrites, of principal cells, and it has Kuffler (1953) and Hartline and Ratliff been suggested that it is generated by the (1957) have clearly established the phenomaction upon these elements of short axon cells enon of lateral inhibition at a retinal level in in the LGD which in turn are activated by the eye of cat and limulus respectively. recurrent collaterals from the axons of prinMETHOD cipal cells (Vastola, in prep.). This mechThese observations were made on cats with anism is believed to represent the most probable interpretation of the following observa- inter-collicular transections of the brain stem tions: (1) after-positivity and its associated which had been prepared for the initial surinhibition may be elicited by antidromic as gery with as small amounts of Surital or well as by orthodromic stimulation of the Trilene (trichlorethylene) as possible. No LGD (Vastola 1959); (2) the inhibitory differences in results attributable to differeffects of after-positivity elicited by a condi- ences in anaesthetic were noted except that tioning stimulus to one optic nerve may be visual radiation spike responses to repetitive seen in the response to testing stimulation of optic nerve stimulation were generally of the other optic nerve. Since the two eyes in higher amplitude when Trilene was used. Electhe cat project in large measure to different trical stimuli were delivered to the contraportions of the LGD (Vastola (in prep.) for lateral optic nerve by 2 silver electrodes, one review of anatomical and electrophysiological encircling the optic nerve just behind the evidence), the latter observation constitutes globe and the other thrust into the center of strong evidence against the hypothesis that the nerve. Separate stimulators were used for inhibitory hyper-polarization is a true positive conditioning and test stimuli respectively. after-potential of the kind seen, for example, Each stimulator was led to its own isolation in the action potential of peripheral nerve transformer. The secondary coils of the transformers were connected in series with a stimfibers. The experiments to be described below ulating electrode at each end. In all experwere performed in order to study the action iments the extra-ocular muscles and intraof inhibitory hyper-polarization when both orbital fatty tissue were removed, and the [ 399 ]

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globe was left intact. The LGD was probed in a vertical direction through intact cortex with a double-barrelled glass capillary electrode filled with 3M NaC1 and connected by saline bridges to 2 calomel half-cells which led to an American Electronics Laboratories D C amplifier. The tip of one barrel was broken away from the other for a distance of 1.5 mm. The outside diameter of the lower tip was 75-100 ~. This electrode was placed for max-

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the radiation spike. Lead wires from this electrode were fine enough to permit it to ride freely with the cortex during respiratory movements. The amplified responses were displayed by the oscilloscope in the usual manner. An u p w a r d deflection in all records figured in this report signals negativity at the lower electrode tip. It may be noted that electrodes as large as those described above record the activity of m a n y neuronal elements.

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Fig. 1 Relationship between amplitude of conditioning after-positivity and amplitude of testing radiation spike with fixed conditioning-test stimulus interval. Inserts show typical records from a representative experiment-short time constant for cortical responses, clots mark test post-synaptie spike recorded in LGD and visual radiation fibers, faster components filtered out of LGD response s. Graphs from 2 different experiments-coordinates in arbitrary units, each point at o r a t e y gives average spike amplitude for all responses with eonditioning after-positivity of amplitude between y and y -~ 1, average number of experimental values per point is 12.

imum amplitude of the post-synaptic response, which usually meant that the lower tip was in the u p p e r half of the LGD. The visual radiation spike was recorded with a bipolar electrode made of 2 nichrome wires, 50 ~ in diameter, which were insulated to their tips and cemented together so that one tip projected about 1 ram. beyond the other. This electrode was inserted by hand vertically into the visual cortex and placed for maximum amplitude of

Expressions used in this report such as "radiation spike' ', for example, should, therefore, be understood to refer to the summed action spikes of m a n y visual radiation fibers. In most experiments the conditioning stimulus strength was 1.5-2 times larger than the testing stimulus strength but was usually submaximal as measured by the amplitude of the post-synaptic spike recorded in both the LGD and visual radiation fibers.

MONOCULAR I N H I B I T I O N RESULTS

The inserts of figure 1 show representative records from an experiment in which the conditioning-test stimulus interval was fixed and the amplitude of the radiation spike response to the test stimulus measured as a function of the amplitude of the conditioning after-positivity. The radiation spike has been found to be a much more sensitive indicator of inhibition than the cell body spike, and a detailed discussion of this phenomenon will be presented in another report. The radiation spike in the records of the cortical response may be identified as the first upward deflection with a latency of 1.6-2.2 msec. This latency comprises a conduction time of 0.8-1.0 msec. to the LGD, 0.5-0.7 msec. delay in the LGD between arrival of the tract spike and beginning of the 1st post-synaptic spike and a conduction time of 0.3-0.5 msec. to the visual cortex. These figures are the same as those previously reported by Bishop and O'Leary (1938). In most preparations after-positivity showed variation in amplitude from response to response, and for this type of experiment maximal variability was desirable. This variability may be related in some instances to changes in amplitude of the accompanying post-synaptic spike recorded in the visual radiation fibers, and, in accord with the mechanism for after-positivity suggested above, this may be ascribed to changes in number of active inhibitory short axon cells due to spontaneous variability in number of principal cell elements discharged by the constant conditioning stimulus. In other instances, however, as in the insert of figure 1, conditioning afterpositivity is not clearly related to the amplitude of the conditioning post-synaptic spike, and this case is believed to represent the inherent variability of response of the short axon cells. There is, in other words, independent variability of post-synaptic response at each of the two types of synapses in the suggested mechanism for after-positivity. The relationship shown in the insert of figure 1 between the amplitude of the test radiation spike and the amplitude of conditioning afterpositivity is clear and typical of the observations made in most experiments. The two

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graphs are from different experiments and demonstrate the same relationship. Maximal depression of the test radiation spike was found to occur at conditioning-test stimulus intervals of 30-50 msec., when the conditioning after-positivity was maximal. Marshall and Talbot (1940) found similar values for this interval when recording the post-synaptic spike response in the LGD. The complete course of recovery of the radiation spike amplitude closely resembles the course of conditioning after-positivity, as was found to be the case when the conditioning and test stimuli were applied to different optic nerves (Vastola, in prep.). The most dramatic expressions of inhibition were elicited by a conditioning stimulus delivered during the course of repetitive test

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Fig. 2 Depression of repetitive radiation spike responses assoeiated with after-positivity elicited by single interposed stimulus of 3.6 times higher strength. Short time constant for cortical responses. A-cortical response to single testing stimulus at 1/see. on fast time line to show radiation spike as first upward deflection with latency = 2 reset.; B and C - - to show close correspondence in magnitude and course between depression and after-positivity.

stimulation. In figure 2, B depression of the radiation spike response to repetitive stimulation paralleled closely the course of conditioning after-positivity. In figure 2, C depression did not occur when the conditioning stimulus was not followed by after-positivity. In experiments of the kind shown in figure 3 an attempt was made to simulate more closely the type of pre-synaptic activity which the LGD receives during photic stimulation of

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the retina. The resting spontaneous activity of a group of retinal ganglion cells in the dark ( K u f f l e r 1953) was represented by continuous stimulation of the optic nerve at 15 per sec. Photic activation of some of these ganglion ceils was represented by an interjected burst of stimuli of much smaller strength at 200-250 per sec. The stimuli used for continuous stimulation at the slow frequency elicited radiation spikes when delivered at ] per sec. which were 3-4 times larger than

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CORTEX Fig. 3 Depression of radiation spike responses at 15/see. during after-positivity accompanying stimulation at higher frequency but lower strength. Radiation spike response to smaller stimulus at 1/sec. about 75 per cent smaller than that to greater stimulus at 1/see. LGD records show responses to testing stimuli at 15/see. alone and interrupted by conditioning stimulation at 2,~n/sec. Cortical records, with short time constant, show radiation spike responses at 15/sec. alon~ ~m 3 typical examples of depression following

n. m,*orposed burst at 200/see. LGD and cortical rccoLds made in same experiment a short time apart.

those elicited by the smaller stimuli when delivered at the same rate. The geniculate records show that after-positivity was elicited at the beginning o f the b u r s t at 250 per sec. althourh it had disappeared from the respons~'s at 15 per see., and in the cortical records depression of the radiation spikes ,~;licited at the s l o w e r f r e q u e n c y is seen to ac, ,)mpany this after-positivity. DISCUSSION E x p e r i m e n t s of the kind illustrated in this report a p p e a r to establish the f a c t t h a t the

inhibitory effects which accompany afterpositivity elicited by stimulation of a given set of fibers in one optic ucrve are exerted upon the principal geniculate neurons innervated both by some fraction of this set (fig. 1 and 2) and by some larger set of fibers in the same nerve (fig. 3). This finding may be added to our observation that the inhibitory effects of after-positivity are also exerted upon principal cells innervated by fibers in the other optic nerve. There would seem to be, therefore, extensive propagation of after-positivity throughout the LGD following the discharge of a relatively small portfim of its principal cells. The mechanism of propagation may be different, but in its eff~,cts, at least, it resembles the inhibitory phenomena described in the retina by K u f f l e r (1953) and IIartline and Ratliff (1957). As in the case of retinal ganglion cells, changes in the patterns of geniculate activity represent the effects of inhibitory as well as excitatory proeesses, and it may be supposed ttmt inhibition would act most effectively upon those principal cells receiving a minimum of synaptic excitation by way of optic tract fibers. In the case of any given pattern of optic nerve activity, the condition of minimal synaptic excitation would probably hold for those principal cells outside the field of innervation by the given set of active tract fibers. In the experiment of figure 3 the afterpositivity produced by the sudden increase in frequency of optic nerve firing from 15 to 250 per sec. may be considered part of the onresponse of geniculate e]ements, and its appearance under these experimental conditions suggests that it may occur also u n d e r the more natural circumstances of retinal stimulation by light. I t has been found that the amplitude of this after-positivity depends to an important degree upon the magnitude of the change in frequency, and a report of a study of this relationship is now in preparation. SUMMARY ]. The inhibitory effects which accompany after-positivity elicited in the LGD by stimulation of a set of fibers in one optic nerve have been found to spread within and beyond

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the field of principal geniculate neurons in- tire Naehschwankung im corpus geniculatum laterale hervorgerufen. Die Hemmwirkungen, nervated by that set of optic nerve fibers. 2. The amplitude of after-positivity pro- welche diese begleiten, warden untersueht und vides an approximate measure of the degree es wurde gefunden, dass sic sieh innerhalb und fiber die Grenzen des Gebietes yon Geniculaof inhibition. ausbreiteten, 3. It is suggested that changes in the pat- tum-Hauptneuronen hinaus tern of geniculate activity following changes welche dureh diese Optikus-Fasergruppe inin the pattern of optic nerve activity reflect nerviert werden. 2. Die Amplitude der positiven Nachthe action of inhibitory as well as excitatory processes and that inhibition is most effect- schwankung gibt ein ungefiihres Mass der ively exerted upon elements receiving a mi- Grades der Hemmwirkung. 3. Es wird gefolgert, dass Ver~inderungen nimum of excitatory synaptic stimulation. in der Geniculatum-Aktivit~it in der Folge R~SUM~ yon Anderungen der Optikus-Aktivit~it nicht 1. Les effets inhibiteurs accompagnant la nur erregende sondern auch hemmende Prophase de positivit~ tardive dans le corps ge- zesse widerspiegeln, und dass Hemmung am nouill~ lateral ~ la suite de stimulations de wirkungsvollsten auf diejenigen Elemente fibres dans un des nerfs optiques s'~tendent ausgeiibt wird welche ein Minimum yon errel'int~rieur et au-del~ du champ des neu- gender synaptischer Stimulation empfangen. rones du ganglion g~nicul~ innerv~ par les This investigation was supported in part by fibres optiques stimul~es. Research Grant B-1086 from the National Institutes 2. L'amplitude de la d~fl~xion positive of Health, Public Health Service, Bethesda, Marydonne une mesure approximative du degr~ land. d'inhibition. REFERENCES 3. L'auteur sugg~re que les changements BISHOP, G. H. and O'LEARY, J. L. Potential records dans le mode d'activit~ du corps genouill~ from the optic cortex of the cat. J. Neurophysiol., la suite des changements dans le mode d'ac1938, I : 391-404. tivit~ du nerf opti~ue refl~tent l'action de HARTLmE, H. K. and RATLIFF, F. Inhibitory interaction of receptor units in the eye of Limulus. processus aussi bien inhibiteur que excitateur J. Gen. Physiol., 1957, 40: 357-376. et que l'inhibition est particuli~rement effi- KUFFLER, K. W. Discharge patterns and functional organization of mammalian retina. J. Neurocace sur les 616ments nerveux qui ne recoiphysiol., 1953, 16: 38-68. vent qu'un minimum de stimulation synapti- MARSHALL, W. and TALBOT, S. A. Recovery cycle of que excitatrice. the lateral geniculate of the nembutalized cat. ZUSAMMENFASSUNG

1. Durch Stimulation einer Gruppe yon Fasern eines nervous opticus wird eine posi-

Amer. J. Physiol., 1940, !Z9: 417-418. VASTOLA, E. F. After-positivlty in the lateral geniculate body. J. Neurophy.~iol., 1959, ~2: 258-272. ~rASTOLA, E. F. Binocular inhibition in the lateral geniculate body. (In preparation.)

l~eferenee: VASTOLA, E. F. Monocular inhibition in the lateral geniculate body. EEG Clin. Neurophysiol., 1960, 12: 399-403.