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We have studied the effects of interictal epileptiform discharges originating from the striate cortex on the development of the receptive field characteristics of neurons in the lateral geniculate nucleus (LGNd) and superior colliculus (SC) in neonatal rabbits. The paroxysmal discharges were generated by twice-daily injections of penicillin into an implanted cannula. Control injections of penicillin + penicillinase were given to the other striate cortex of the same animal. Similar experimental procedures were used to study the effect of such projected discharges on the LGNd neurons in adult rabbit. The results of the first experiment show that cortical epileptiform discharges, initiated in neonatal rabbits 7--9 days of age and continuing to 20--25 days of age, retard the normal development of LGNd cells. There was an abnormal increase of indefinite cells, cells failing to respond to any light stimulation, and a concurrent decrease of cells with concentric cells was still present in adult rabbits which had interictal discharges in the striate cortex limited to the period of 7--9 days to 21--25 days of age. The fourth experiment shows that the interictal discharges in neonatal rabbits do not affect the normal receptive field development of neurons in the SC. The present results demonstrate that asymptomatic interictal epileptiform discharges, produced without focal structural damages in immature brain, can affect the development of neuronal connectivity. These results may have some clinical implications in relation to our understanding about the learning and developmental disabilities exhibited in children who had episodic seizure discharges.

Receptive field properties of cells in the dorsal lateral geniculate nucleus (LGNd) were examined in 3 groups of rabbits, each subjected to monocular visual deprivation by lid suture at differing age periods. Monocular deprivation occurring from 6--8 to 20--25 days of age affected the normal development of LGNd receptive fields. A significant proportion of the cells in the deprived LGNd were either unresponsive to visual stimulation or had vague, indefinite receptive fields. Significantly fewer cells with uniform fields were found in the deprived LGNd than in the control. Percentages of concentric, motion and directional cells did not differ between the deprived and control LGNd. The diameters of receptive fields for concentric cells with sustained response properties, however, were smaller in the deprived than in the control LGNd. When deprivation was continued to 87--121 days of age, the percentage of uniform, indefinite and non-responsive cells found in the deprived LGNd approached more normal levels. Percentages of concentric, motion and directional cells were also normal. Monocular deprivation commencing at 21--22 days of age also had disruptive effects on LGNd receptive field organization, as reflected in the lower percentage of uniform and increased percentages of indefinite and non-responsive cells. These deficits, however, were not as severe as those seen in the animals deprived at an early age. A fourth group of adult rabbits subjected to monocular lid suture showed no such detrimental deficits in receptive field organization. These results demonstrated that visual deprivation affects the predominantly monocular LGNd of the rabbit, and that a critical period exists for such effects.

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.