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The purpose of this study was to determine the selectivity with which polyspecific antibodies directed against large retinal ganglion cells destroy axons in the cat's optic nerve. Immune serum prepared against large ganglion cells isolated from ox retinas was injected into 1 eye of each of 2 cats. After more than 1 month, the cats were perfused with mixed aldehydes and the optic nerves were prepared for transmission electron microscopy. On the basis of a large sample of micrographs of transverse thin sections, we estimated that each of the nerves that issued from treated eyes contained approximately 62,500 necrotic fibers, amounting to 42-46% of the total fiber population in 1 case and 39-42% in the other. The diameters of 2900-5000 intact axons from each of 4 nerves (2 from immune-treated eyes and 2 from untreated eyes) were measured. Comparisons of histograms of axon diameter for nerves from treated and untreated eyes revealed that 90-100% of large axons with diameters above 3.5-4.0 micron were eliminated by the antibodies. Between 65 and 70% of medium-sized fibers were also eliminated. The number of small axons--those with diameters less than 1.2-1.6 micron--did not differ appreciably from normal. These results suggest that the immune serum destroyed virtually all alpha cell axons and a substantial fraction of beta cell axons but did not reduce the number of small fibers that largely stem from the gamma class of retinal ganglion cells.

In the companion study ( Dev. Brain Res. , 34 (1987) 223–233), we showed that a monocular injection of antibodies against ox large retinal ganglion cells produces a 53% (low concentration) to 82% (high concentration) loss of Y-cells in lateral geniculate nucleus (LGN) layers A and A 1 that receive inputs from the antibody-injected eye. At the same time, the percentage of LGN X-cells is unaffected. In the present study, we investigated the effect of this monocular antibody-induced reduction of LGN Y-cells on the development of ocular dominance in striate cortex. Four-week-old kittens were given an intraocular injection of either a low (110 μg/33 μl volume) or a high (333 μg/33 μl volume) concentration of antibodies and single-cell recordings were carried out in striate cortex 33–65 weeks later. Following an injection of either antibody concentration, we found only slight abnormalities in striate cortex ocular dominance compared to normal adult cats. There was a small, but significant, decrease in the percentage of binocularly driven cells and a concomitant increase in the percentage of cells driven exclusively by the normal or control-injected eye. No ocular dominance abnormalities were found in kittens injected monocularly with control γ-globulins, indicating that the changes are due to effects of the antibodies. The changes in cortical ocular dominance produced by early antibody treatment are very different from those produced by rearing with monocular deprivation (MD) despite a similar loss of LGN Y-cells in the two conditions. This suggests that an initial (primary) monocular loss of LGN Y-cells in young kittens is not sufficient to alter cortical ocular dominance in a manner similar to that found after MD. The results thus argue against the hypothesis that the MD-induced loss of response to the deprived eye in striate cortex is secondary to a Y-cell loss in the LGN.

A comparison was made between penicillin- and bicuculline-induced epileptiform activity. Aqueous solutions of either penicillin or bicuculline were applied to striate cortex of rabbit pups, and the electroencephalogram was monitored. Applications were made twice daily for 14 consecutive days beginning on postnatal day 8–9. During this time period, interictal spikes generated by bicuculline and penicillin displayed similar properties in most respects. However, the morphology of spikes induced by each convulsant was different.

Studies have shown that normal development of receptive field properties in striate cortex and lateral geniculate nucleus (LGN) of the rabbit is severely altered in the presence of penicillin-induced disruption of cortical neuronal activity. We wished to replicate these studies using a different convulsant drug in order to rule out possible effects due to the penicillin drug itself. Aqueous bicuculline was injected twice daily into a cannula implanted over the monocular region of one striate cortex. Drug administration was initiated on postnatal day 8–9 and was discontinued either on postnatal day 19–24 or on postnatal day 24–30 for studies of the LGN and striate cortex, respectively. Coincidental with the bicuculline injections, control solutions were similarly applied to the monocular region of the contralateral striate cortex. Single-unit recordings made from LGN ipsilateral to bicuculline-treated cortex revealed normal percentages of receptive field types. However, in single-unit recordings made from bicuculline-treated striate cortex, an abnormal percentage distribution of receptive field types was found. In such cortex there was an unusually high proportion of no-response type cells and a substantially reduced proportion of oriented type cells. These developmental abnormalities are virtually the same as those found in the striate cortex of similarly reared animals treated with penicillin. Our present results lend support to our previous conclusion that in the rabbit, disruption of orderly neuronal activity in the geniculostriate system has a detrimental effect on the development of receptive fields in this system.

We studied the long-term effects of early epileptiform activity on the development of receptive fields in the visual cortex of the rabbit. Aqueous penicillin was injected twice daily into a cannula implanted over the monocular region of one visual cortex. Drug administration was initiated on postnatal day 8–9 and was discontinued on postnatal day 24–30. Coincidental with the penicillin injections a mixture of penicillin and penicillinase was similarly applied to the monocular visual region of the contralateral (control) cortex. Following each drug administration interictal epileptiform activity was observed only from the penicillin-treated (epileptic) cortex. Single-unit recordings were made in the visual cortex 5 or 11 months after the drug-treatment period. In both 5-month and 11-month postepileptic cortex, cell samples from areas adjacent to the cannula site showed abnormal percentages of receptive field types relative to control cortex percentages. After 5 months a low proportion of oriented type cells and a high proportion of no response and indefinite type cells were found. After 11 months a low proportion of oriented type cells was also found but the proportion of no response and indefinite type cells was normal; however, an unusually high proportion of non-oriented type cells was now evident. These results indicate that although previously epileptic visual cortex eventually develops a normal complement of cells with specific receptive fields, the quantitative distribution of those cells with regard to their various functional specificity remains abnormal.

We examined the effects of early epileptiform activity on development of visuocortical receptive fields in the rabbit. Aqueous penicillin was injected twice a day into a cannula implanted over the monocular area of one visual cortex. Drug administration was begun on postnatal day 8-9 and continued until postnatal day 24-30. Concomitant with the penicillin injections a mixture of penicillin and penicillinase was similarly applied to the monocular area of the contralateral control cortex. Interictal discharges were routinely observed only from the penicillin-treated or epileptic cortex. Single-unit recordings made on postnatal day 25-31 revealed that in the neuronal population adjacent to the cortical penicillin focus percentages of receptive field types were severely altered relative to control cortex percentages. Epileptic cortex showed an abnormally high percentage of no response type cells together with an abnormally low percentage of complex and oriented-directional type cells. These abnormalities were greater closer to the penicillin focus than further from it. Epileptic visual cortex receptive field percentages are compared with those for the neonatal rabbit and the rabbit subjected to early monocular deprivation. One interpretation of our results is that development of complex and oriented-directional type cells is impeded by epileptogenic disruption of organized geniculostriate activity.