Hippocampal CA1 neuronal properties in genetically epilepsy-prone rats: evidence for increased excitation

The genetically epilepsy prone rats (GEPRs) are abnormally susceptible to seizures with a variety of treatments and can be used as a model to study generalized seizure predisposition involving the brainstem and forebrain structures. We investigated the basic membrane and synaptic properties of hippocampal CA1 cells in Sprague-Dawley (SD) rats and GEPRs. Several differences in cellular properties were observed in the GEPRs. These include an increase in membrane input resistance and reduced spike frequency adaptation in the majority of GEPR cells. A decrease in the amount of current required to elicit a 5-mV EPSP was observed in the GEPR. A marked increase in excitability with paired pulse stimulation was also observed in GEPRs both in extracellular population spikes and intracellular EPSPs. Applying bicuculline, a GABAA antagonist, markedly increased paired pulse facilitation of the population spike in SD rats but in GEPRs produced only a minimal effect on facilitation. This difference suggests reduced GABAA-mediated inhibition in GEPR hippocampus with paired pulse stimulation. Several factors could interact or act independently to produce these effects because the epileptic phenotype in GEPRs is regulated by multiple genes.