Abstracts

Rationale: Stroke is the dominant cause of epilepsy in the elderly. Our previous studies using the cortical photothrombosis model of stroke suggest that a higher percentage of aged rats develop limbic seizures after infarction compared to young adults animals.. In order to study the relationship of aging, cortical infarction, and limbic epileptogenesis, we characterized resting membrane potential (RMP) and single action potential (AP) threshold, GABAA receptor (GABAAR)-mediated inhibitory synaptic transmission and AMPA/KA-mediated excitatory synaptic transmission in CA3 pyramidal neurons in control 4 and 20 month old male Fischer 344 rats and one week after infarction. Methods: AMPA/kainite and GABAAR-mediated whole-cell currents (sIPSCs, mIPSCs, sEPSCs, mEPSCs) were recorded from CA3 pyramidal neurons in transverse dorsal hippocampal slices from 4 and 20 mo old control and lesioned animals with visualized voltage-clamp. RMP and AP measurements were obtained in whole-cell current-clamp mode. Recordings were obtained from the ipsilateral hemisphere of lesioned animals. The covariance of age and infarction on the electrophysiological data were measured with two-way ANOVA. Post-hoc group comparisons were performed with the Bonferonni test. Results: RMP was depolarized in aged lesioned animals (p=0.006); infarction resulted in a lower AP threshold in both young adult and aged animals (p=0.009). There were no significant effects on sIPSCs, whereas 10-90% rise time of mIPSCs was increased in infarcted animals (p=0.038). Median amplitude of sEPSCs was increased in infarcted animals (0.032), whereas sEPSC frequency was increased by age, infarction, and their interaction (p<0.001). No effects were seen on mEPSCs. Conclusions: These findings indicate that aging and cortical infarction variably affect intrinsic membrane properties and GABAAR and AMPA/KA functioning in CA3 pyramidal neurons. These plastic changes likely contribute to the increased excitatory tone of the hippocampus following permanent sensorimotor cortical ischemic infarction and predispose it to mechanisms of limbic epileptogenesis.