John M. Crook

Evidence for a contribution of lateral inhibition to orientation tuning and direction selectivity in cat visual cortex: reversible inactivation of functionally characterized sites combined with neuroanatomical tracing techniques

We have previously reported that cells in cat areas 17 and 18 can show increases in response to non‐optimal orientations or directions, commensurate with a loss of inhibition, during inactivation of laterally remote, visuotopically corresponding sites by iontophoresis of γ‐aminobutyric acid (GABA). We now present anatomical evidence for inhibitory projections from inactivation sites to recording sites where ‘disinhibitory’ effects were elicited. We made microinjections of [3H]‐nipecotic acid, which selectively exploits the GABA re‐uptake mechanism, < 100 μm from recording sites where cells had shown either an increase in response to non‐optimal orientations during inactivation of a cross‐orientation site (n = 2) or an increase in response to the non‐preferred direction during inactivation of an iso‐orientation site with opposite direction preference (n = 5). Retrogradely labelled GABAergic neurons were detected autoradiographically and their distribution was reconstructed from series of horizontal sections. In every case, radiolabelled cells were found in the vicinity of the inactivation site (three to six within 150 μm). The injection and inactivation sites were located in layers II/III–IV and their horizontal separation ranged from 400 to 560 μm. In another experiment, iontophoresis of biocytin at an inactivation site in layer III labelled two large basket cells with terminals in close proximity to cross‐orientation recording sites in layers II/III where disinhibitory effects on orientation tuning had been elicited. We argue that the inactivation of inhibitory projections from inactivation to recording sites made a major contribution to the observed effects by reducing the strength of inhibition during non‐optimal stimulation in recurrently connected excitatory neurons presynaptic to a recorded cell. The results provide further evidence that cortical orientation tuning and direction selectivity are sharpened, respectively, by cross‐orientation inhibition and iso‐orientation inhibition between cells with opposite direction preferences.

GABA-induced inactivation of functionally characterized sites in cat striate cortex: Effects on orientation tuning and direction selectivity

Microiontophoresis of gamma-aminobutyric acid (GABA) was used to reversibly inactivate small sites of defined orientation/direction specificity in layers II-IV of cat area 17 while single cells were recorded in the same area at a horizontal distance of approximately 350-700 microns. We compared the effect of inactivating iso-orientation sites (where orientation preference was within 22.5 deg) and cross-orientation sites (where it differed by 45-90 deg) on orientation tuning and directionality. The influence of iso-orientation inactivation was tested in 33 cells, seven of which were subjected to alternate inactivation of two iso-orientation sites with opposite direction preference. Of the resulting 40 inactivations, only two (5%) caused significant changes in orientation tuning, whereas 26 (65%) elicited effects on directionality: namely, an increase or a decrease in response to a cells preferred direction when its direction preference was the same as that at an inactivation site, and an increase in response to a cells nonpreferred direction when its direction preference was opposite that at an inactivation site. It is argued that the decreases in response to the preferred direction reflected a reduction in the strength of intracortical iso-orientation excitatory connections, while the increases in response were due to the loss of iso-orientation inhibition. Of 35 cells subjected to cross-orientation inactivation, only six (17%) showed an effect on directionality, whereas 21 (60%) showed significant broadening of orientation tuning, with an increase in mean tuning width at half-height of 126%. The effects on orientation tuning were due to increases in response to nonoptimal orientations. Changes in directionality also resulted from increased responses (to preferred or nonpreferred directions) and were always accompanied by broadening of tuning. Thus, the effects of cross-orientation inactivation were presumably due to the loss of a cross-orientation inhibitory input that contributes mainly to orientation tuning by suppressing responses to nonoptimal orientations. Differential effects of iso-orientation and cross-orientation inactivation could be elicited in the same cell or in different cells from the same inactivation site. The results suggest the involvement of three different intracortical processes in the generation of orientation tuning and direction selectivity in area 17: (1) suppression of responses to nonoptimal orientations and directions as a result of cross-orientation inhibition and iso-orientation inhibition between cells with opposite direction preferences; (2) amplification of responses to optimal stimuli via iso-orientation excitatory connections; and (3) regulation of cortical amplification via iso-orientation inhibition.

GABA-induced remote inactivation reveals cross-orientation inhibition in the cat striate cortex

SummaryWe investigated the contributions of lateral intracortical connections to the orientation tuning of area 17 cells using micro-iontophoresis of the inhibitory transmitter gamma-aminobutyric acid (GABA) to inactivate small cortical sites in the vicinity of a recorded cell. GABA was ejected from an array of micropipettes each with an average horizontal distance of 500 μm from the recording site. Of 54 cells tested, 33 showed a reduction and 3 a loss of orientation selectivity due to an increase in responses to non-optimal orientations during GABA inactivation. The response to the optimal orientation remained constant in more than half of the cells and increased or decreased in others. Given that a complete cycle of orientations occupies a tangential distance of 1000 μm, the observed broadening of orientation tuning is presumably due to GABA-mediated inactivation of inhibitory interneurones with different preferred orientations from those of their target cell.

Influence of GABA-induced remote inactivation on the orientation tuning of cells in area 18 of feline visual cortex: a comparison with area 17.

We have investigated the effect of iontophoretically applying the inhibitory transmitter gamma-aminobutyric acid (GABA) through four pipettes, each located at a horizontal distance of some 500-600 microns from the recording site, on the orientation tuning of cells in areas 17 and 18 of the cat visual cortex for moving the stationary flash-presented bar stimuli. Forty-five of 74 cells tested in area 18 (61%) showed a significant (greater than 25%) increase in orientation tuning width (at half the maximum response) during GABA application, which reflected an increase in response to non-optimal orientations. The mean orientation tuning width of these cells increased by 79%, and the ratio of responses to the orientation orthogonal to the optimum and to the optimum increased from 0.16 to 0.46. The results were similar to those from area 17, in which 36 of 54 cells (66%) showed significant broadening of orientation tuning during GABA application, with a 90% increase in mean tuning width and an increase in the relative response to the orientation orthogonal to the optimum from 0.17 to 0.42. The distributions of cells in areas 17 and 18 with respect to the magnitude of GABA-induced effects on orientation tuning width were not significantly different (mean increase in tuning width: area 17, 102%; area 18, 87%). Although most cells were tested only with moving bars, comparable effects of remote GABA application on orientation tuning were observed when stationary flash-presented bars were used. Of 11 cells thus tested in area 18, seven showed significantly broader tuning during GABA application, with a 132% increase in mean tuning width. In some 25% of cells in each area which showed a significant effect of GABA application on orientation tuning the response to at least one non-optimal orientation exceeded, during GABA application, the response to the previous optimum. There was essentially no correlation between the changes in orientation tuning and changes in the level of spontaneous activity or in the response to the optimum orientation during GABA application. Thus, an increase in the general excitability of recorded cells or the loss of an unspecific inhibitory input cannot account for the effects of GABA application on orientation tuning. Remote GABA application presumably inactivated cells with different preferred orientations from that of the recorded cell. It is thus argued that the observed broadening of orientation tuning during GABA application reflected the loss of an inhibitory input tuned to non-optimal orientations.(ABSTRACT TRUNCATED AT 400 WORDS)

The neurophysiological correlates of colour and brightness contrast in lateral geniculate neurons

SummaryThe colour of an object is changed by surround colours so that the perceived colour is shifted in a direction complementary to the surround colour. To investigate the physiological mechanism underlying this phenomenon, we recorded from 260 neurons in the parvo-cellular lateral geniculate nucleus (P-LGN) of anaesthetized monkeys (Macaca fascicularis), and measured their responses to 1.0–2.0° diameter spots of equiluminant light of various spectral composition, centered over their receptive field (spectral response function, SRF). Five classes of colour opponent neurons and two groups of light inhibited cells were distinguished following the classification proposed by Creutzfeldt et al. (1979). In each cell we repeated the SRF measurement while an outer surround (inner diameter 5°, outer diameter 20°) was continuously illuminated with blue (452 nm) or red (664 nm) light of the same luminance as the center spots. The 1.0–1.5° gap between the center and the surround was illuminated with a dim white background light (0.5–1cd/m2). During blue surround illumination, neurons with an excitatory input from S-or M-cones (narrowand wide-band/short-wavelength sensitive cells, NSand WS-cells, respectively) showed a strong attenuation of responses to blue and green center spots, while their maintained discharge rate (MDR) increased. During red surround illumination the on-minus-off-responses of NS- and WS-cells showed a clear increment. L-cone excited WL-cells (wide-band/long-wavelength sensitive) showed a decrement of on-responses to red, yellow and green center spots during red surround illumination and, in the majority, also an increment of MDR. The response attenuation of narrow-band/long-wavelength sensitive (NL)-cellls was more variable, but their on-minus-off-responses were also clearly reduced in the average during red surrounds. Blue surround illumination affected WL-cell responses little and less consistently than those of NL-cells, but often broadened the SRF also in the WL-cells towards shorter wavelengths. The M-cone excited and S-cone suppressed WM-cells were strongly suppressed by blue but only little affected by red surround illumination. The changes of spectral responsiveness came out clearly in the group averages of the different cell classes, but snowed some variation between individual cells in each group. The zero-crossing wavelengths derived from on-minus-off-responses were also characteristically shifted towards wavelengths complementary to those of the surround. The direction of changes of spectral responsiveness of P-LGN-cells are thus consistent with psychophysical colour contrast and colour induction effects which imply that light of one spectral region in the surround reduces the contribution of light from that same spectral region in the (broad band or composite) object colour. Surrounds of any colour also decrease the brightness of a central coloured or achromatic light (darkness induction). We calculated the population response of P-LGN-units by summing the activity of all WS-, WM- and WL-cells and subtracting that of all NS- and NL-cells. The SRF of this population response closely resembled the spectral brightness function for equiluminous lights rather than the photopic luminosity function. With red or blue surrounds, this population SRF was lowered nearly parallel across the whole spectrum to about 0.7 of the amplitude of the control. In a psychophysical test on 4 observers we estimated the darkness induction of an equiluminous surround in a stimulus arrangement identical to the neurophysiological experiment, and found a brightness reduction for white, blue, green and red center stimuli to 0.5–0.7 of the brightness values without surround. This indicates that the neurophysiological results may be directly related to perception, and that P-LGN-cells not only signal for chroma but also for brightness, but in different combinations. The results indicate that both an additive (direct excitation or suppression of activity) and a multiplicative mechanism (change of gain control) must be involved in brightness and colour contrast perception. As mechanisms for the surround effects horizontal cell interactions appear not to be sufficient, and a direct adaptive effect on receptors feeding positive or negative (opponent) signals into the ganglion cells receptive fields by straylight from the surround must be seriously considered. This will be examined in the following companion paper. The results indicate that changes of spectral and brightness responses in a colour contrast situation sufficient to explain corresponding changes in perception are found already in geniculate neurons and their retinal afferents. This applies to mechanisms for colour constancy as well in as much as they are related to colour contrast.

Combined physiological-anatomical approaches to study lateral inhibition

In the visual cortex, large basket cells form the cellular basis of long-range lateral inhibition. The present paper focuses on combinations of methods with which large basket cells can be studied in the context of extensive neuronal representations. In the first approach, the topographic relationship between large basket axons and known functional representations such as orientation, direction, and ocular dominance is analysed. Functional mapping is carried out using extracellular electrode recordings or optical imaging of intrinsic signals followed by 3-dimensional anatomical reconstruction of biocytin stained large basket cells in the same regions. In the second approach, the contribution of lateral inhibition to orientation and direction selectivity is assessed using the GABA inactivation paradigm and direct inhibitory projections from the inactivation to recording sites are demonstrated with biocytin staining and injections of [3H]nipecotic acid, a radioactive marker for GABAergic cells. The limitation of these approaches is that they can only be used in cortical regions which lie on the surface of the brain.

Neurophysiological Correlates of Colour Induction on White Surfaces.

Coloured light surrounding a white surface of about equal luminance makes the white surface appear illuminated with an unsaturated light of the complementary colour. In an attempt to discover the neurophysiological basis of such colour induction, we recorded from spectrally opponent cells of the parvocellular layers of the lateral geniculate nucleus (P‐LGN) of anaesthetized macaques. Only cells with wide‐band (W) spectral sensitivity in the short (S) or long wavelength (L) part of the spectrum (WS, WL) are excited by white spots of light centred on their receptive field. Cells with narrow‐band (N) spectral sensitivity (NS, NL) and light‐inhibited (L1) cells are inhibited by white light. Therefore, it is likely that the code for white is contained in a balanced excitation of the W cells. The effects of continuous illumination of remote surrounds with different wavelengths on the responses to achromatic light stimuli were investigated. Responses [on minus maintained discharge rate (MDR) or on‐minus‐off] were determined for white spots (1–3° diameter) flashed on the receptive field centre, presented either alone or in the presence of an annular surround of equal luminance (inner diameter 5°; outer diameter 20°). During red surround illumination the responses of WL cells to white spots tended to be reduced as were those of WS cells during blue surround illumination. Surround illumination with the opponent colour had more variable effects, neither WS nor WL cells showing a significant alteration of their mean response to white during surround illumination with opponent light. Response alterations were to a large extent due to changes in MDR, which increased in WS cells during blue surround illumination and in WL cells during red surround illumination. It is argued that the surround effects on centre responses are due to intraocular stray light rather than lateral connections in the retina. The surround effects also depended to some extent on the size of the test spot. L1 cells and the very rare parvocellular panchromatic on‐cells showed no chromatic response changes during coloured surround illumination. Inasmuch as the excitation of WS cells, either alone or in combination with NS cell activation, is involved in coding for green and blue, and that of WL cells, in combination with NL cell activation, is involved in coding for red and yellow in perception, the shift of excitation towards one or the other W cell group indicates relatively more red or green signals in the white response, consistent with and in the same direction as colour induction. In addition, the summed population response of WS and WL cells is decreased during surround illumination with any colour including white. This is related to brightness decrease during surround illumination in perception.

Velocity invariance of preferred axis of motion for single spot stimuli in simple cells of cat striate cortex

Directional tuning for motion of a long bar and a spot was compared quantitatively over a wide range of velocities in 23 simple cells of cat striate cortex whose “on” and “off” receptive field subregions had been mapped with optimally oriented, stationary flash-presented bars. Tuning curves were derived using stimuli whose polarity of contrast was appropriate for the dominant receptive field subregion of each cell (i.e. light stimuli for on-subregions and dark stimuli for off-subregions); stimulus sweep was centred accurately on the centre of that subregion. Bar stimuli were of optimal width, and spot diameter was equal to the width of the bars. In all simple cells, preferred axis of motion for a long bar was invariant with velocity, being orthogonal to preferred orientation, as assessed with a stationary flash-presented bar. In 20 of 23 simple cells, preferred axis for spot motion was approximately orthogonal to that for bar motion (i.e., parallel to preferred orientation) at all velocities tested, including those just above threshold for spot stimuli. However, tuning for the spot became sharper as velocity was increased, due to an increase in response to the spot moving along the preferred axis and a decrease in response to spot motion along other axes, including the preferred axis for the bar. Both preferred and upper cut-off velocity were consistently higher for spot than for bar motion. The remaining 3 simple cells showed no response to spot motion at any velocity, and their preferred axis of motion for the shortest bar which evoked a consistent response was the same as that for a long bar. We conclude that simple cells respond to motion of a spot per se and not just to its oriented components, and that in most simple cells preferred axis for spot motion is genuinely approximately orthogonal to that for motion of a long bar. A spatio-temporal filter model incorporating intracortical feedforward facilitation along the long axis of the receptive field can account for the observed differences in axis preference and velocity sensitivity for spot and bar motion.