Abstracts

Acute ischemic infarction of the neocortex is typically followed by functional reorganization of cortical circuitry. In the periinfarction area, GABAergic-mediated inhibitory neurotransmission is impaired and neuronal activity is enhanced, changes that may predispose to epileptogenesis and poststroke epilepsy. We used the model of cortical photothrombosis and brain infarction to examine the changes of GABA[sub]A[/sub] receptor-mediated inhibitory synaptic input to pyramidal neurons of layer II-III of ipsilateral sensorimotor cortex 1-2 mm lateral to the infarct 7-10 days after photothrombosis of 4-month-old Fischer 344 rats., Whole cell patch-clamp techniques were used to record postsynaptic currents (PSCs), and spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) of pyramidal neurons of layer II-III of ipsilateral sensorimotor cortex 1-2 mm lateral to the infarct. Analysis was performed on PSCs and sIPSCs recorded from 46 pyramidal neurons (lesioned, n=23; control, n=23) and mIPSCs recorded from 33 of the 46 pyramidal neurons (lesioned, n=18; control, n=15)., In lesioned animals, PSC amplitude was unchanged compared with controls, whereas decreases were observed for sIPSC ([sim]23% lower than that of control, 24.93 [underline]+[/underline] 2.23 pA in lesioned vs.32.54 [underline]+[/underline]2.98 pA in controls) and mIPSC ([sim]22% lower than that of control, 20.12[plusmn]1.27 pA in lesioned vs. 25.72[plusmn]2.50 pA in controls) amplitude. There was an increase in the 10-90% rise time of PSCs ([sim]31% longer than that of control), sIPSCs ([sim]36% longer than that of control ) and mIPSCs ([sim] 29% longer than that of control ) in lesioned animals, whereas decay time constant and charge transfer were not significantly different compared with controls. There was an increase in PSC frequency ([sim] 41% higher than that of control, 3.10[plusmn]0.28 Hz in lesioned vs. 2.17[plusmn]0.23 Hz in controls) in lesioned animals, whereas sIPSC ([sim]21% higher) and mIPSC ([sim]18% higher) frequency demonstrated only trends toward increases. Additionally, sIPSC and mIPSC conductance was decreased (23% and 21.7%, respectively)., These findings indicate that cortical photothrombosis results in alterations of GABAergic inhibition of pyramidal neurons in close proximity to the infarct, which likely contribute to the increased excitatory tone of the area following ischemic infarction and may predispose it to the mechanisms of epileptogenesis., (Supported by R01 NS046015 to KMK.)