In this study, we used in vitro electrophysiology along with immunohistochemistry and molecular techniques to study the subiculum - a limbic structure that gates the information flow from and to the hippocampus - in pilocarpine-treated epileptic rats. Comparative data were obtained from age-matched nonepileptic controls (NEC). Subicular neurons in hippocampal-entorhinal cortex (EC) slices of epileptic rats were: (i) hyperexcitable when activated by CA1 or EC inputs; and (ii) generated spontaneous postsynaptic potentials at higher frequencies than NEC cells. Analysis of pharmacologically isolated, GABAA receptor-mediated inhibitory postsynaptic potentials revealed more positive reversal potentials in epileptic tissue (-67.8 ± 6.3 mV, n = 16 vs. -74.8 ± 3.6 mV in NEC, n = 13; P <0.001) combined with a reduction in peak conductance (17.6 ± 11.3 nS vs. 41.1 ± 26.7 nS in NEC; P <0.003). These electrophysiological data correlated in the epileptic subiculum with (i) reduced levels of mRNA expression and immunoreactivity of the neuron-specific potassium-chloride cotransporter 2; (ii) decreased number of parvalbumin-positive cells; and (iii) increased synaptophysin (a putative marker of sprouting) immunoreactivity. These findings identify an increase in network excitability within the subiculum of pilocarpine-treated, epileptic rats and point at a reduction in inhibition as an underlying mechanism.
- Potassium-chloride contransporter 2
- Temporal lobe epilepsy
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