Topographic plasticity in primary visual cortex is mediated by local corticocortical connections

Abstract

The placement of monocular laser lesions in the adult cat retina produces a lesion projection zone (LPZ) in primary visual cortex (V1) in which the majority of neurons have a normally located receptive field (RF) for stimulation of the intact eye and an ectopically located RF (displaced to intact retina at the edge of the lesion) for stimulation of the lesioned eye. Animals that had such lesions for 14-85 d were studied under halothane and nitrous oxide anesthesia with conventional neurophysiological recording techniques and stimulation of moving light bars. Previous work suggested that a candidate source of input, which could account for the development of the ectopic RFs, was long-range horizontal connections within V1. The critical contribution of such input was examined by placing a pipette containing the neurotoxin kainic acid at a site in the normal V1 visual representation that overlapped with the ectopic RF recorded at a site within the LPZ. Continuation of well defined responses to stimulation of the intact eye served as a control against direct effects of the kainic acid at the LPZ recording site. In six of seven cases examined, kainic acid deactivation of neurons at the injection site blocked responsiveness to lesioned-eye stimulation at the ectopic RF for the LPZ recording site. We therefore conclude that long-range horizontal projections contribute to the dominant input underlying the capacity for retinal lesion-induced plasticity in V1.

Figure 6.

Presentation of case VL36 in which the KA injection failed to affect the response at the LPZ recording site to stimulation of the lesioned (left) eye ectopic RF. A, Grid presentation of the essential RFs and the lesion position. LOD, Left optic disk. B, C, Response histograms summated over 10 presentations and representative individual raw recordings from a single stimulus presentation for recordings from the pipette at the injection site, indicating that the KA injection was successful in suppressing neural activity at this site. D, E, Response histograms for recordings from the main recording site to optimal stimulation with a moving bar via the left (lesioned) and right (intact) eye, respectively. No change to response at the lesioned eye was evident at the LPZ site after the KA injection. A clear statistically significant response, although reduced in magnitude, was maintained for stimulation of the intact eye (five bins around peak response; 11 min, z = 5.43, p << 0.001; 93 min, z = 5.99, p << 0.001). The means and 95% confidence limits of spontaneous activity are shown to the right of the peristimulus response histograms (see Fig. 3. for interpretation).

Figure 1.

Summary of a recording experiment (VL25) demonstrating that the input to LPZ neurons with an ectopic RF was provided by the normal representation of that area of visual space in V1. A and B show RFs (left) and recording positions on section outlines (right) before injection of KA at site d (in A). C presents postinjection RFs recorded at positions in the same electrode penetration as in B. The visual projections of RFs and the outline of the lesion (in gray to indicate relative position only for the intact eye) have been transposed from the tangent screen onto Lambert equal-area projection coordinates and corrected for binocular vergence error by aligning the relative positions of the areas centralae. In B and C, the alphabetical order of recording sites indicates the chronological sequence of recordings, with recordings being made from site g over the period of the injection. After complete neural deactivation at the injection site (which had a normal RF, site d, matching the position of the ectopic RF at site g), stimulation through the lesioned eye in the region of the ectopic RF no longer activated responses at site g, but responses elicited through stimulation of the intact eye were unchanged. Subsequent recordings at positions h, j, and k also failed to elicit responses to stimulation through the lesioned eye while showing responses with normally positioned RFs to stimulation through the intact eye. LOD, Left optic disk. D--F show three projections of the position and extent of the laser lesion in the left eye, as seen in the fundus view (D), in visual projection coordinates (E, Lambert equal-area projection; 10 degree grid; VM, vertical meridian; HM, horizontal meridian) and as would be represented on the medial surface of right occipital cortex [F, dorsomedial view with projection modified from Tusa et al. (1978); orientation indicated by the coordinate axes; d, dorsal; l, lateral; c, caudal].

Figure 2.

Essential elements of case VL9 in which the determinations of responsiveness were made qualitatively, following the format of VL25 (Fig. 1). In the grid projections, the filled objects denote the multiunit RFs obtained by stimulation of the left (lesioned) eye and the right (intact) eye at the LPZ recording site studied over the period of KA injections. The neuronal RF recorded through the pipette at the KA injection site is shown unfilled. As in other cases, the receptive field to stimulation of the left eye was ectopic, displaced beyond the boundary of the lesion (gray outline). After two submicroliter KA injections, responsiveness at the injection site and the LPZ site and stimulation of the left (lesioned) eye were lost. Responses to stimulation of the right (intact) eye were maintained throughout (monitored for 2.5 hr after the KA injections). VM, Vertical meridian; HM, horizontal meridian.

Figure 3.

Deactivation of an ectopic RF for neurons located at recording site d in the LPZ demonstrated with quantitative methods (experiment VL30). A-E follow the format of Figure 1 and show the location (A) of recording and KA injection sites (sections are 3 mm apart) and the corresponding positions of RFs determined separately for intact eye (D, E) and lesioned eye (B, C) stimulation. In these projections, the lesion (indicated as relative position only for the intact eye), left-eye optic disk (LOD), and area centralis (small filled circle) are shown. To deactivate the injection site, five small KA injections were made over a period of 130 min (see Materials and Methods). Peristimulus response histograms recorded at site g are shown pre-KA and post-KA injection for stimulation through the intact (G) and lesioned (F) eyes. To the right of the first histogram for each series, a gray bar indicates the range and mean (dark line) of spontaneous activity. This range is given as ± 1.96 the SD (or the 95% confidence interval; by chance, 1 in 20 histograms bins will marginally exceed these limits). Compared with the initial recordings, spontaneous activity 160-167 min after the first KA injection is slightly reduced, with a maintenance of responses to stimulation through the intact eye and a loss of responsiveness to stimulation of the lesioned eye. For these determinations, the stimulus was a 5 × 0.5° light bar, moved in the indicated directions across the approximate position of the respective RFs at 15°/sec. Response histograms were summed over 10 presentations, interleaved across stimulus conditions (including conditions not shown in this summary). Below the histograms is a sample of the multiunit discharge to a single stimulus presentation; arrows indicate the discriminator level.

Figure 4.

Experiment VL26. Deactivation of an ectopic RF of a discriminated LPZ single neuron (C, site d) after a single KA injection at the site of neurons is shown, with matched RFs in the normal V1 map (B, D, site z). The neural responses shown by the poststimulus time histograms in F and G were collected with the electrode at site d and are illustrated for a single orientation (summed over 10 repeats). Responses to stimulation of the intact eye decreased a little over the course of the experiment but remained distinct and reached a high rate. In contrast, driven responses to stimulation through the lesioned eye (delivered over the ectopic field) were not apparent after the KA injection. The mean and 95% confidence interval (see Fig. 3) of spontaneous activity are shown by the gray bar at the right of the histograms; at 4 and 24 min after KA injection, insufficient data were available from the relevant epochs to establish these values. Presentation conventions are as for Figure 3; velocity of stimulus, 3°/sec.

Figure 5.

Summary of cases VL34 (A) and VL41 (B), which were examined quantitatively. The presentation of the RF positions follows the format of Figure 2. Quantification of the effect of KA injection is summarized by polar plots of net peak discharge rates (spikes per second minus the mean spontaneous rate; 400 and 100 msec peak periods, respectively). The polar angle represents the direction of movement of a light bar centered on the relevant RF. The open circle represents a net rate of zero (equivalent to mean spontaneous rate), and the grayed annulus has a radius of 1.96× the SD of the spontaneous discharge rate (for the post-KA epochs, which in both cases was the higher rate), indicating the 95% confidence limit (see Fig. 3). In both cases, visually evoked responses to stimulation of the ectopic field were lost or reduced to insignificant levels after KA injection, whereas responses to stimulation of the intact eye remained clear. In case VL41 (B), a strong response to stimulation of the intact eye remained after the KA injection. However, the orientation preference of the response was lost, whereas in case VL34 (A), it was maintained. LOD, Left optic disk.