GABA mediated inhibitory processes in the function of the geniculo-striate system.
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Biomedical subjects
A M Sillito
Publications and source records attributed to A M Sillito.
The action of the putative neurotransmitters N-acetylaspartylglutamate and L-homocysteate in cat dorsal lateral geniculate nucleus.
1. We have examined the actions and pharmacology of two putative optic nerve transmitters, N-acetylaspartylglutamate (NAAG) and L-homocysteic acid (L-HCA), in the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses obtained to iontophoretic application of these substances with those elicited by visual stimulation and application of specific N-methyl-D-aspartate (NMDA) and non-NMDA receptor agonists. The relative effects of the selective NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were tested on these responses. 2. There was a pronounced contrast between the influence of iontophoretically applied NAAG and L-HCA on dLGN cells. Iontophoretic application of NAAG [ejection current range 75-200 nA (mean 125 nA)] evoked either no effect (17/37), or very weak and sluggish excitatory (16/37) or inhibitory (4/37) effects. Conversely, L-HCA application [current range 25-136 nA (mean 67 nA)] elicited brisk and powerful excitatory responses (32/32) that were comparable with those produced by visual stimulation and iontophoresis of NMDA, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 3. Responses to L-HCA were selectively antagonized by application of the NMDA receptor antagonist CPP but were generally much less affected by the non-NMDA receptor antagonist CNQX. The weak and inconsistent responses to NAAG were not compatible with an evaluation of antagonist effects. 4. CPP application at dose levels selective for NMDA with respect to kainate and AMPA did not exert equal effects on L-HCA and NMDA. Whereas the mean responses to L-HCA were reduced to 32% of control for Y cells and 21% for X cells, those to NMDA were 11 and 11%, respectively. However, the level of reduction of the visual response for X and Y cells was very similar to that of L-HCA, visual responses being reduced to 35 and 22% of control for Y and X cells. 5. CNQX application reduced the visual response level of Y cells to 64% of control and that of X cells to 65%. The mean level for the L-HCA response of Y cells was 106% of control; the mean for X cells, 79%, was substantially below control. The responses to kainate and AMPA were reduced to a much greater extent. 6. The data suggest that it is unlikely that NAAG is the optic nerve transmitter.(ABSTRACT TRUNCATED AT 400 WORDS)
6-Cyano-7-nitroquinoxaline-2,3-dione↗
A re-appraisal of the role of layer VI of the visual cortex in the generation of cortical end inhibition.
These experiments examine the effect of blockade of layer VI of the cat striate cortex on the length tuning of hypercomplex cells in the overlying layers II, III and IV. It has previously been suggested that local inactivation of layer VI results in the complete loss of length selectivity in all hypercomplex cells in layers II, III and IV above the blocked region, by removal of an inhibitory mechanism within layer IV, driven from layer VI. However, we have found that, using iontophoretic application of the inhibitory substance GABA to block the activity of layer VI, 29% of hypercomplex cells were unaffected by blockade of the underlying layer VI. The predominant effect on hypercomplex cells was a reduction in visual responsiveness, seen in 71% of cells, with responses reduced on average by 43%. In 50% of these cells (35% of the population) this reduction was apparently specific to responses to the optimum bar length; responses to longer stimuli were unaffected. Iontophoretic application of the potent GABAA analogue muscimol in layer VI showed a similar spectrum of effects on hypercomplex cells. In these cases, however, the cortical blockade was slowly increased to encompass the recorded cell. In each case, any decreases in length selectivity were also the result of a decreased visual responsiveness. Thus, decreases in length selectivity seen when using either GABA or muscimol were almost exclusively the result of decreased responsiveness to the optimal length of bar stimulus, rather than an increase in response to non-optimal, long stimuli. This suggests the loss of a facilitatory influence from layer VI to layer IV, rather than the loss of inhibition.
Animals↗
The length summation properties of layer VI cells in the visual cortex and hypercomplex cell end zone inhibition.
Layer VI of the visual cortex has been considered to be dominated by cells with very long receptive fields, typically summing to 8 degrees or more. We have re-examined this issue in a series of experiments in which the length tuning profiles of layer VI cells in the cat visual cortex have been quantitatively determined. Responses were assessed to optimally oriented bars of light of varying length drifted over the receptive field. The lengths were varied on a randomised interleaved sequence. Although our data confirm the presence of long field cells in layer VI, only 24% of a population of 119 cells had fields greater than 6 degrees in length. Fields greater than 8 degrees were only seen in 17% of cells. 61% of the population of cells had fields showing summation to 4 degrees or less with a mean length of 2.8 degrees (+/-0.15 sem). In this "short field" group, 18% had fields of 1 degrees or less. We observed 7 cells with rapid initial spatial summation up to 1 degree, followed by clear end zone inhibition. It has been recently suggested on the basis of localised inactivation experiments, that layer VI cells with long (greater than 8 degrees) fields may provide the drive to inhibitory interneurones in layer IV generating hypercomplex cell end zone inhibition. This observation is difficult to equate with evidence indicating that hypercomplex cell end zone inhibition reflects a mechanism showing maximal summation at lengths in the region of 2.8 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cholinergic enhancement of direction selectivity in the visual cortex of the cat.
Acetylcholine and acetyl-beta-methacholine were applied iontophoretically to single cells in the feline striate cortex. The directional bias of the visual response to an optimally oriented stimulus was assessed quantitatively, before and during drug application. For the great majority of the cells that were affected by the drugs, selectivity was either unchanged (28/60, 47%) or increased (21/60, 35%). In particular, directional bias increased for 36% (12/33) of the cells that were facilitated by acetylcholine or acetyl-beta-methacholine and 43% (nine out of 21) of those that were inhibited, as compared with 9% (three out of 33) and 24% (five out of 21) for which the bias decreased. Six additional cells, of which three showed a reduced selectivity, were apparently excited by the drugs, in that the background discharge level was greatly increased with a concomitant decrease in signal-to-noise ratio. It is known that cholinergic input has the potential to enhance cortical function, by facilitating both the excitatory and the inhibitory components of the neuronal circuit. Our data show that this combination of effects can precipitate an enhancement of selectivity as well as of response magnitude.
Acetylcholine↗
The length-response properties of cells in the feline dorsal lateral geniculate nucleus.
1. In this report we have systematically examined the length-response properties of a large population of cells recorded in the cat dorsal lateral geniculate nucleus (dLGN). The responses of A laminae dLGN cells were assessed by the use of conventional single-unit extracellular recording techniques. The length preference of these cells was examined by plotting multihistogram length tuning curves to moving bars of light. Bar length was randomized in an interleaved fashion under computer control. The other stimulus parameters were standardized within the limits of those routinely used to assess the length preference of cortical cells. 2. The majority of cells (186/198), whose length-response properties are considered in detail in this report, exhibited strong centre-surround antagonism and a mean degree of length tuning equivalent to, or exceeding, that seen in most cortical hypercomplex cells (71 +/- 1.18%, S.E.M., n = 186). 3. The values for X cells (74 +/- 1.41%, S.E.M., n = 100) and Y cells (67 +/- 2.13%, S.E.M., n = 74) were very similar, as were those of the on-centre (71 +/- 1.51%, S.E.M., n = 123) and off-centre (71 +/- 1.85%, S.E.M., n = 63) subgroups. 4. A distinct subgroup of the Y cell population was identified. These comprised the remaining twelve out of the 198 cells examined and their response properties were sufficiently distinct to merit classification as a discrete subpopulation of cells which we have termed nlY cells. They were characterized by very poor levels of both centre-surround antagonism and length tuning, and were most frequently encountered close to laminar borders. Their response properties have been described in detail elsewhere. 5. We quantitatively compared the degree of length tuning seen with moving bars to the strength of centre-surround antagonism assessed with flashing spots. The degree of length tuning did not necessarily follow the level of centre-surround antagonism. 6. Examination of the effects of unilaterally extending bar length to one or other side of the receptive field did not reveal the type of asymmetry frequently seen in cortical hypercomplex cells. 7. The high degree of length tuning seen in this study underlines the potential importance of geniculate response properties to the generation of the length-response properties of cortical hypercomplex cells. The findings are discussed in relation to the synaptic mechanisms contributing to the generation of length tuning at subcortical and cortical levels.
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A specific subgroup of non-length tuned relay cells in the feline dorsal lateral geniculate nucleus.
Length tuning was first described for the "hypercomplex cell category" in the visual cortex. However it has subsequently become apparent that cells in the dorsal lateral geniculate nucleus (dLGN) also exhibit a high degree of length tuning and that for the majority of the population this matches or exceeds that associated with cortical hypercomplex cells (Cleland et al. 1983; Jones and Sillito 1987). In this paper we describe a distinct subpopulation of dLGN Y cells that lack length tuning. These cells were also characterised by poor centre-surround antagonism, and tended to be located close to laminar borders. They appeared to constitute 25% of the Y cell population. Following recent evidence showing relay cells to be powerfully excited by acetylcholine, and inhibitory interneurones to be inhibited, we have examined the responses of these non-length tuned cells to iontophoretic application of acetylcholine. Their brisk excitatory responses suggest that these cells are in fact relay cells. Their presence raises the possibility of a discrete non-length tuned component to the geniculate input to the cortex, and has potentially important implications for the way in which synaptic processes contributing to the length tuning profiles of visual cortical cells are modelled.
Acetylcholine↗
The contribution of the non-N-methyl-D-aspartate group of excitatory amino acid receptors to retinogeniculate transmission in the cat.
The N-methyl-D-aspartate receptor antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid and the non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione have been iontophoretically applied to cells in the cat dorsal lateral geniculate nucleus and their effects on the visual response compared. The objective was to examine the possibility of both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors being involved in the transfer of the retinal input to X and Y cells in the dorsal lateral geniculate nucleus. The results show that selective blockade of either N-methyl-D-aspartate receptors or non-N-methyl-D-aspartate receptors can block the visual response of both X and Y cells. Overall, the most potent reductions of visual responses across the population of cells studied were obtained with the N-methyl-D-aspartate receptor antagonist with X cells showing a slightly greater reduction on average (80%) than Y cells (66%). The relatively smaller overall reductions in visual responses obtained with the non-N-methyl-D-aspartate receptor blockade reflected the lower levels of blockade that were compatible with selectivity using iontophoretic applications of 6-cyano-7-nitroquinoxaline-2,3-dione. It is concluded that N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors are critically involved in the visual response of both "on" and "off" centre X and Y cells.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Dependence of retinogeniculate transmission in cat on NMDA receptors.
1. We have examined the possibility that N-methyl-D-aspartate (NMDA) receptors may be involved in the visual response of relay cells in the cat dorsal lateral geniculate nucleus (dLGN). The selective NMDA receptor antagonists D-2-amino-5-phosphonovalerate (APV) and 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) have been iontophoretically applied to X and Y cells in the dLGN and their effects on the visual response to a light spot flashed within the receptive field center determined. 2. The antagonist effects were assessed at ejection current levels producing a selective blockade of the responses to iontophoretically applied NMDA with respect to those elicited by the non-NMDA receptor agonists quisqualate and kainate. These selective effects were determined in an experimental paradigm where the visual response and responses to NMDA and the non-NMDA receptor agonists were compared in the same test run. The data refer to a total population of 52 cells (28 X, 24 Y). 3. Application of APV abolished or greatly reduced the visual responses of both X and Y cells. The mean percentage reduction in the visual response for the X cells studied was 59 +/- 10% (SE; n = 7) and for the Y cells 66 +/- 8% (SE; n = 11). Both the early onset transient and the sustained component of the visual response to the flashed stimulus were equally affected. 4. The antagonist CPP produced a similar pattern of effect to APV, substantially reducing or abolishing the visual response in both X and Y cells.(ABSTRACT TRUNCATED AT 250 WORDS)
2-Amino-5-phosphonovalerate↗
The binocular input to cells in the feline dorsal lateral geniculate nucleus (dLGN).
1. Cells in the A laminae of the dorsal lateral geniculate nucleus receive their primary innervation from either the contralateral (A) or ipsilateral (A1) eye. This paper provides evidence concerning the responses they give to visual stimulation of what is commonly regarded as the ineffective or non-dominant eye. It also examines the contribution of the corticofugal input to these responses. 2. Cells were identified and classified according to their responses to stimulation of the dominant eye receptive field. This was then occluded and the corresponding location in the non-dominant eye field stimulated by a moving bar. Out of fifty-seven cells examined forty-three (75%) gave a response to stimulation of the non-dominant eye. There was no obvious difference between the effects on X and Y cells in these experiments. 3. In most cases (thirty-seven) the response involved an inhibition of the resting discharge level, but three cells gave a mixed excitatory and inhibitory response and three a pure excitatory response. All the responses were weak and only revealed by prolonged periods of averaging (20-100 trials). 4. Ionophoretic application of the GABA antagonist N-methyl-bicuculline (NMB) blocked the visually elicited inhibitory effects and in most cases (twenty-seven out of thirty-two tested) revealed an excitatory response. Out of a further eight cells previously unresponsive to the non-dominant eye, NMB application revealed excitatory responses in three. 5. Increasing background discharge levels and cell excitability by ionophoretic application of either acetylcholine or the excitatory amino acid, quisqualate, did not eliminate inhibitory responses and did not reveal excitatory responses. We suggest that the visually driven non-dominant eye suppression of the background discharge involves a GABA-mediated inhibitory input which masks an underlying excitatory input. 6. An excitatory non-dominant eye response could potentially derive from the influence of the corticofugal projection. However, removal of the corticofugal input by aspiration of areas 17 and 18 did not reduce either the excitatory or the inhibitory components of the response. 7. In the absence of corticofugal input all cells tested (fourteen) exhibited a non-dominant eye response and all studied during NMB application (eleven) gave an excitatory response. The primary effect of removing the corticofugal input appeared to involve the loss of a 'damping' influence on the excitatory and inhibitory responses, such that they were more easily revealed. The significance of these findings is discussed.
Action Potentials↗
The modulation of the retinal relay to the cortex in the dorsal lateral geniculate nucleus.
The translation of the retinal input through the dorsal lateral geniculate nucleus (dLGN) to the visual cortex is highly dependent on a range of influences. This article reviews the available evidence. One of the influences, the corticofugal projection to the dLGN from layer VI of the visual cortex, provides a synaptic input which in magnitude exceeds that from the retina. This makes direct synaptic contact on relay cells and the intrinsic and perigeniculate inhibitory interneurones influencing their activity. The corticofugal system appears to be spatially organised in such a way that for any given region in the dLGN, there is a central zone comprising an overlying field with facilitatory effect, and a surrounding zone with inhibitory influence. The extent to which these overlap is open to question at present. The inhibitory effect of the corticofugal projection can be clearly seen in its contribution to the length tuning of dLGN cells when tested with drifting bars. On average dLGN cells exhibit a very high degree of length tuning, matching that of cortical hypercomplex cells. Removal of the corticofugal influence causes a radical reduction in this, shifting the mean reduction in peak response with increasing bar length from 71% to 43%. One consequence of this corticofugal effect is that the selectivity of the dLGN cell receptive field towards stimuli spatially restricted to the vicinity of the centre mechanism, is as good for moving bars as it is for stationary flashing spots. The retinal output to dLGN relay cells appears to be mediated by excitatory amino acid receptors, of both NMDA and non-NMDA categories. The non-NMDA receptors appear to provide an initial level of depolarisation which enables the operation of the voltage dependent NMDA receptor channels. The NMDA receptor however sits as a critical gate regulating the transmission of retinal information in the dLGN, when it is blocked visual responses are virtually eliminated. Its voltage dependency makes it crucially dependent on the complex pattern of excitatory and inhibitory influences from the cortex and the "non-specific" modulatory influence of the cholinergic system.
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Continuity of orientation columns between superficial and deep laminae of the cat primary visual cortex.
1. Recent reports of a marked and consistent dislocation between orientation columns in the superficial and deep layers of cat striate cortex (Bauer, 1982, 1983) directly contradict the traditional view of the system (Hubel & Wiesel, 1962). This has considerable implications for our current understanding of cortical organization, and in order to clarify the issue we have carried out experiments to test the continuity of the columnar system with depth, in central regions of area 17. 2. In twenty-four penetrations, eighteen of which were placed as perpendicular as possible to the surface of the cortex, orientation preference was assessed at regular intervals both qualitatively and using a randomly interleaved quantitative technique. The distribution of preferred orientations was analysed with reference to a detailed histological reconstruction of the electrode track, including the location of laminar boundaries and the course of radial tiers of cells and capillaries. 3. From a further series of eighteen near-perpendicular penetrations, the change in average orientation between one superficial and one deep layer recording site was compared with the deviation of the track from perpendicular to the surface and hence parallel to the orientation columns. 4. In penetrations perpendicular to the surface of the cortex, orientation preference showed little variation between superficial and deep laminae. In oblique penetrations, preferred orientation generally changed according to a single, smooth trend. Those irregularities that were encountered were confined to oblique penetrations, and were distributed throughout the cortical laminae. 5. In conclusion, our evidence does not support the presence of a systematic discontinuity with depth within the orientation columnar system. It is therefore entirely consistent with earlier evidence on the subject.
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Modulatory and inhibitory processes in the visual cortex.
The functional role of three putative neurotransmitter systems in the visual cortex is compared; the GABAergic inhibitory interneurons, the interneurones containing somatostatin and the cholinergic input originating from the nucleus basalis of Meynert (nbM). Evidence is presented to support the role of GABAergic processes in the generation of the functional structure of the visual cortex and the view that the cholinergic input exerts a neuromodulatory influence enhancing stimulus selective responses. Although the neuropeptide somatostatin produces facilitatory and inhibitory effects on visual cortical cells there is no clear functional pattern to its action. The possible significance of this data and the interaction of SSt with GABA is discussed in the light of evidence that they may coexist in some cells.
Acetylcholine↗
Inhibitory mechanisms influencing complex cell orientation selectivity and their modification at high resting discharge levels.
1. These experiments have investigated the contribution made by GABA-mediated inhibitory processes to the orientation tuning of complex cells in the cat's striate cortex. The GABA antagonist bicuculline has been ionophoretically applied to individual complex cells and the modifications produced in their orientation tuning documented. 2. In terms of the type of change produced in orientation tuning by the application of bicuculline, it seems that there are two categories of complex cells. 3. In one of these categories the orientation selectivity was eliminated during bicuculline application. The excitatory input to these cells would therefore appear to be non-orientation specific. Their orientation selectivity is presumably generated by a GABA-mediated inhibitory input. 4. In the other category of complex cells, although the orientation selectivity was decreased during bicuculline application, the cells retained a preference for a range of orientations that was generally centred around the original optimal orientation. It is suggested that for these cells the inhibitory input enhances the orientation tuning of an excitatory input that is already broadly orientation tuned. 5. Comparison of normal orientation tuning curves with those observed during the application of bicuculline provides a basis for estimating the orientation tuning of the GABA-mediated inhibitory input. In all cases, it is clear that at normal resting discharge levels, orientations either side of the optimal, and not those centred on the optimal, generate the most powerful inhibitory input. 6. These results would seem to be best explained by inhibitory interconnexions between cortical columns sensitive to different orientations. This type of lateral interaction between columns may serve to enhance the contrast in the orientation domain for the cortical representation of a specific stimulus orientation. 7. Increasing the resting discharge level of a complex cell, without blocking the action of GABA appeared to increase the gain of the inhibitory mechanisms acting on the cell. The normal excitatory responses to optimal or near optimal orientations were greatly reduced, or replaced by inhibitory responses, and non-optimal orientations produced only inhibitory responses. These inhibitory effects were blocked on the context of other observations in the literature. It is tentatively suggested that the interneurones providing the inhibitory drive to complex cells receive an input from recurrent collaterals of the recipient complex cells. Their other inputs would derive from neighbouring colums and from the afferent input to the parent column. The inputs from neighbouring columns would mediate the lateral inhibitory interactions in the orientation domain, and the recurrent collateral feed-back the decreased responsiveness at high resting discharge levels.
Animals↗
Action of exitatory amino acid antagonists on the retinal input to the cat lateral geniculate body [proceedings].
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Acetylcholine↗
Inhibition and the normal ocular dominance distribution in cat visual cortex [proceedings].
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Animals↗
Inhibition and velocity tuning in the cat visual cortex [proceedings].
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Animals↗
Inhibitory processes underlying the directional specificity of simple, complex and hypercomplex cells in the cat's visual cortex.
1. The iontophoretic application of bicuculline, an antagonist of GABA, the putative inhibitory transmitter in the visual cortex, has been used to examine the contribution of post-synaptic inhibitory processes to the directional selectivity of simple, complex and hypercomplex cells in the cat's striate cortex.2. The directional selectivity of simple cells was significantly reduced or eliminated during the iontophoretic application of bicuculline. This supports the view that the selectivity is derived from the action of a GABA-mediated post-synaptic inhibitory input modifying their response to a non-directionally specific excitatory input.3. Complex cells were subdivided into three categories on the basis of the action of iontophoretically applied bicuculline on their directional selectivity, receptive field characteristics and distribution in terms of cortical layer. They are referred to as type ;1', ;2' and ;3' complex cells.4. The directional specificity of type ;1' complex cells was eliminated during the iontophoretic application of bicuculline. It seems likely, therefore, that they receive a non-directionally specific excitatory input and that, as for simple cells, the directional specificity derives from the action of a GABA-mediated post-synaptic inhibitory input. No type ;1' complex cells were recorded below layer IV.5. The directional specificity of type ;2' complex cells was unaffected by the iontophoretic application of bicuculline, despite increases in response magnitude, a block of the action of iontophoretically applied GABA and, in some cases, changes in other receptive field properties. It is suggested that these cells receive a directionally specific excitatory input. The type ;2' complex cells were found both superficial and deep to layer IV with the majority in layer V.6. Type ;3' complex cells appear to have very similar receptive field properties to those of the cells described by other workers as projecting to the superior colliculus. They were found predominantly in layer V. Their directional specificity was not eliminated by the iontophoretic application of bicuculline. However, they exhibited a powerful suppression of the resting discharge in response to stimulus motion in the non-preferred direction. Iontophoretic application of ammonium ions revealed a small excitatory response in place of the suppression. It appears from these observations that the directional specificity of the type ;3' complex cells could be determined, at least in part, by an inhibitory process which is not GABA-mediated.7. The directional specificity of hypercomplex cells found in layers II and III was unaffected by the iontophoretic application of bicuculline, and they showed no suppression of their background discharge level in response to stimulus motion in the non-preferred direction. This evidence is consistent with the view that they receive a directionally specific excitatory input.
Action Potentials↗