EVIDENCE OF INCREASED EXCITABILITY IN GEPR HIPPOCAMPUS PRECEDING DEVELOPMENT OF SEIZURE SUSCEPTIBILITY

The genetically epilepsy-prone rat (GEPR) provides a valuable model to study the mechanism of neonatal seizure susceptibility because seizur e predisposition in GEPRs is determined by factors present from birth. We have previously shown that reduced afterhyperpolarization (AHP), r educed spike frequency adaptation and increased excitation with repeti tive stimulation are present in the adult GEPRs. To investigate whethe r these abnormalities are present at birth or appear at the time when GEPRs show seizure susceptibility and to elucidate whether these abnor malities were a consequence of seizure experience (the adult rats prev iously tested were induced to seize in three tests), we studied the me mbrane and synaptic properties of CA3 hippocampal neurons in preseizin g offspring of GEPR-9s (seizure naive GEPRs). Electrophysiological rec ordings were done in the in vitro brain slice preparation during three different stages of early postnatal development (postnatal day (P) 7- 10, P12-15 and P18-28) in GEPRs and compared to age matched control Sp rague-Dawley (SD) rats. Reduction in AHP amplitude and duration and re duced inhibitory post synaptic potentials (IPSPs) were observed in the CA3 region in ail the three stages tested. Reduction in spike frequen cy adaptation in 40% of CA3 neurons and reduction in fast AHP occurred in the 3rd and 4th weeks of postnatal development in GEPRs. Therefore , our results suggest that reduced synaptic inhibition and increased m embrane excitability in the CA3 circuitry are present from early postn atal development and may represent few of the general cortical feature s that might eventually contribute to development of enhanced seizure susceptibility in developing GEPRs. (C) 1998 Elsevier Science B.V. All rights reserved.