Evidence of increased excitability in GEPR hippocampus preceding development of seizure susceptibility

Abstract 

The genetically epilepsy-prone rat (GEPR) provides a valuable model to study the mechanism of neonatal seizure susceptibility because seizure predisposition in GEPRs is determined by factors present from birth. We have previously shown that reduced afterhyperpolarization (AHP), reduced spike frequency adaptation and increased excitation with repetitive stimulation are present in the adult GEPRs. To investigate whether these abnormalities are present at birth or appear at the time when GEPRs show seizure susceptibility and to elucidate whether these abnormalities were a consequence of seizure experience (the adult rats previously tested were induced to seize in three tests), we studied the membrane and synaptic properties of CA3 hippocampal neurons in preseizing offspring of GEPR-9s (seizure naive GEPRs). Electrophysiological recordings 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 Sprague–Dawley (SD) rats. Reduction in AHP amplitude and duration and reduced inhibitory post synaptic potentials (IPSPs) were observed in the CA3 region in all the three stages tested. Reduction in spike frequency 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 membrane excitability in the CA3 circuitry are present from early postnatal development and may represent few of the general cortical features that might eventually contribute to development of enhanced seizure susceptibility in developing GEPRs.

Keywords:  Genetic epilepsy, Epilepsy, Hippocampus, CA3 neurons, GEPR, Development