Abstracts

RATIONALE: A deficit of GABAergic inhibition is thought to underlie seizures in temporal lobe epilepsy. Although the death of some populations of interneurons is consistent with this hypothesis, the modifications in the surviving inhibitory pathways are poorly understood. The goal of this study was to characterize the physiological properties of interneurons in chronically epileptic animals. METHODS: We have performed recordings from various classes of interneurones in the CA1 area of the hippocampus in slices of pilocarpine-treated rats with spontaneous recurrent limbic seizures. Interneurons were filled with biocytin for post hoc identification. The spontaneous activity of interneurons was recorded in cell attached conditions and the ratio between spontaneous/miniature and GABA-ergic/glutamatergic synaptic currents was measured in the voltage-clamp cofiguration. RESULTS: 3 We report that: 1) 75% of the interneurons fire spontaneously in experimental animals vs. 30% in control animals. 2) The spontaneous firing frequency is increased by 50% in experimental epilepsy. 3) More than 50% of the spontaneous currents is glutamatergic, less than 50% being GABAergic in experimental animals vs. a 20%/80% ratio in control animals; 2) 73% of the spontaneous glutamatergic currents are action potential-dependent, only 27% being recorded in the presence of TTX (both in control and epileptic animals); 3) more than 50% of the spontaneous glutamatergic currents are action potential-dependent, less than 50% being recorded in the presence of TTX (both in control and epileptic animals). These alterations affected all classes of interneurons likewise. CONCLUSIONS: The increased glutamatergic drive, a probable consequence of the sprouting of pyramidal cell axonal collaterals, may explain the hyperactivity of the surviving interneurons. Therefore, there is a reversal of the balance between excitation and inhibition in interneurons in epileptic animals. We conclude that, at least in vitro and outside seizures, the reorganization of the inhibitory pathways results in an increased inhibitory control of principal cells.