REGIONAL DIFFERENCES IN HIPPOCAMPAL EXCITABILITY MANIFESTED BY PAIRED-PULSE STIMULATION OF GENETICALLY EPILEPTIC EL MICE

Hippocampal excitability in El mice was studied by analyzing paired-pu lse 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 m ice. 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 m ice when compared to ddY mice. Phenobarbital (200 mu M) decreased pair ed-pulse ratio (PPR) by 30% in El mice, and bicuculline (1 mu M) incre ased PPR by 80% in ddY mice at 10 ms IPI. These results suggest an int rinsic existence of decreased GABA(A) receptor-mediated inhibition in CA1 of El mice. In dentate gyrus (DG), an increase in paired-pulse fac ilitation of PSs was observed at intermediate IPIs (50-200 ms) in El m ice at both ages, especially at 15 weeks of age, when 52%-increased PP R was recorded. The facilitation was not due to GABA(A) receptor-media ted inhibition and was not age-dependent. In CA3 area, increased paire d-pulse facilitation of PSs and EPSPs over the range of 10-1000 ms IPI s was observed only in the 15-week-old El mice. The age-dependent appe arance of seizure susceptibility was associated with the increase in e xcitatory synaptic transmission in CA3. Our results show that El mice possess excitatory/inhibitory synaptic transmission abnormalities in t he hippocampus that could contribute to seizure predisposition. (C) 19 98 Elsevier Science B.V.