Abstracts

Rationale: Ischemic infarction of the neocortex is typically followed by functional reorganization of cortical circuitry. In the perinfarction area, GABAergic-mediated inhibitory neurotransmission is impaired and neuronal activity is enhanced. Pathophysiological events associated with poststroke epileptogenesis include changes of cortical inhibitory GABAergic interneurons, which result in defective GABAergic inhibition of cortical pyramidal neurons. In order to study the relationship of cortical infarction and cortical epileptogenesis, we examined the changes of GABAA receptor-mediated inhibitory synaptic input to pyramidal neurons of layer V of ipsilateral sensorimotor cortex 1-2 mm lateral to the infarct one month after photothrombosis of 4-month-old Fischer 344 rats. Methods: Voltage-clamp (sIPSCs and mIPSCs) was recorded from layer V pyramidal neurons (n=64) in left sensorimotor cortex from 4 mo control (n=4) and 4 mo lesioned (n=4) animals with visualized patch-clamp. Lesioned animals were recorded ipsilateral to the cortical lesion. All group comparisons of electrophysiological data were assessed using unpaired t-tests, p<0.05. Results: The mean amplitude of sIPSCs was significantly decreased and the interevent interval was significant longer in the 4 mo old lesioned group. Mean and median amplitude of mIPSCs was significantly increased in the 4 mo lesioned group with no change in interevent interval. 10-90% rise time and decay time constants were not significantly changed in the 4 mo lesioned group. Conclusions: These findings indicate that cortical photothrombosis results in alterations of GABAergic inhibition of layerV pyramidal neurons in close proximity to the infarct, which likely contributes to the shift of inhibitory and excitatory tone of the area following ischemic infarction and may predispose it to the mechanisms of cortical epileptogenesis. Supported by NINDS R01NS46015 to KMK.