Regional differences in hippocampal excitability manifested by paired-pulse stimulation of genetically epileptic El mice

Abstract

Hippocampal excitability in El mice was studied by analyzing paired-pulse responses of population excitatory postsynaptic potentials (EPSPs) and population spikes (PSs). In vitro slice preparations from seizure-susceptible adult (15 weeks old) and non-seizure susceptible young (5 weeks old) El mice were compared with age-matched mother strain ddY mice. In CA1 area, paired-pulse inhibition of PSs was reduced by about 50% at 10 ms interpulse interval (IPI) in both 5 and 15 weeks old El mice when compared to ddY mice. Phenobarbital (200 μM) decreased paired-pulse ratio (PPR) by 30% in El mice, and bicuculline (1 μM) increased PPR by 80% in ddY mice at 10 ms IPI. These results suggest an intrinsic existence of decreased GABA A receptor-mediated inhibition in CA1 of El mice. In dentate gyrus (DG), an increase in paired-pulse facilitation of PSs was observed at intermediate IPIs (50–200 ms) in El mice at both ages, especially at 15 weeks of age, when 52%-increased PPR was recorded. The facilitation was not due to GABA A receptor-mediated inhibition and was not age-dependent. In CA3 area, increased paired-pulse facilitation of PSs and EPSPs over the range of 10–1000 ms IPIs was observed only in the 15-week-old El mice. The age-dependent appearance of seizure susceptibility was associated with the increase in excitatory synaptic transmission in CA3. Our results show that El mice possess excitatory/inhibitory synaptic transmission abnormalities in the hippocampus that could contribute to seizure predisposition.