Vigabatrin pre-treatment prevents hilar somatostatin cell loss and the development of interictal spiking activity following sustained simulation of the perforant path

Abstract

Somatostatin-containing neurons in the hilus of the dentate gyrus are known to be exceptionally vulnerable in experimental models of epilepsy, as well as in human temporal lobe epilepsy. The position of these cells in the circuitry of the dentate gyrus is ideal for gating the activation evoked by afferents from the entorhinal cortex. In the present study we have shown that the loss of hilar somatostatin-containing neurons, and the development of interictal spiking activity induced by sustained perforant pathway stimulation can be prevented by high doses (500 mg/kg), but not by low doses (100 mg/kg) of vigabatrin, an irreversible inhibitor of GABA-transaminase.