Abstracts

Ischemic stroke can result in seizure generation and epileptogenesis, the mechanisms of which remain unclear. Changes in neuronal excitation mediated by NMDA receptors have been reported to last as long as 10-17 months in the ipsilateral hemisphere following brain ischemia; however, there is little information available regarding potential changes of non-NMDA type glutamate receptor- mediated synaptic transmission in peri-infarction cortex., Guided by infrared video-microscopy, spontaneous postsynaptic currents (sPSCs), spontaneous excitatory postsynaptic currents (sEPSCs) and miniature sEPSCs (mini-EPSCs) were obtained at holding potential of -70mV by whole-cell voltage-clamp recording from layer V pyramidal neurons of the sensorimotor cortex of 4 mo old F344 rats and 7 days after photothrombotic cortical infarction. Non-NMDA type glutamate receptor-mediated sEPSCs were obtained by including 50[micro]M picrotoxin in the bath medium; these sEPSCs were completely blocked by NBQX. The morphology of pyramidal neurons was verified by biocytin labeling., Inward sPSC amplitude was increased in the photothrombosis group (79.88[underline]+[/underline]0.71 pA) compared with the control group (66.64[underline]+[/underline]0.47 pA) (p[lt]0.001), without changes in frequency, verifying increased excitatory synaptic transmission . Both the frequency and amplitude of sEPSCs were increased in the photothrombosis group (7.43[underline]+[/underline]0.15Hz and 80.5[underline]+[/underline]0.75pA) compared with the control group (6.85[underline]+[/underline]0.12Hz and 67.12[underline]+[/underline]0.54pA) (p[lt]0.001). Finally, TTX-resistant mini-EPSCs were recorded in the presence of both 50[micro]M picrotoxin and 1[micro]M TTX, and analyzed offline for quantitative estimation of the total current mediated by non-NMDA receptors, including frequency, amplitude, rise-time and decay-time., These results indicate that excitatory synaptic transmissions to cortical pyrmidal neurons is enhanced, and that non-NMDA type glutamate receptor-mediated synaptic transmission is altered in cortical areas proximal to the photothrombotic infarct one week after lesioning. These results may contribute to the mechanisms of post-infarction epileptogenesis., (Supported by R01NS046015.)