Temporal lobe epileptogenesis

Project Summary / Abstract Our ultimate goal is to discover causes of seizures in patients with temporal lobe epilepsy. The primary objective of the proposed project is to generate new data on reelin-positive interneurons in the dentate gyrus and test whether their loss is epileptogenic. The specific aims are to: Identify the type of reelin interneuron whose loss correlates with seizure frequency. Test whether loss of reelin interneurons in the dentate gyrus occurs in a large animal model of temporal lobe epilepsy. Test whether reelin-positive interneurons are total molecular layer cells. Measure the strength of synaptic output of reelin interneurons. And test whether loss of reelin causes seizures. To achieve these goals animal models will be evaluated: pilocarpine-treated rats and sea lions with naturally occurring temporal lobe epilepsy. Methods employed will include continuous telemetric video-EEG seizure monitoring, immunocytochemistry, stereology, whole cell recording in hippocampal slices, biocytin labeling, paired recording of unitary inhibitory postsynaptic currents, and prolonged focal brain infusion using mini-osmotic pumps.