Human mesial temporal lobe epilepsy is often associated with changes in the afferent and efferent projections of dentate granule cells. Most important, the granule cell layer suffers less cell loss than the CA fields, which suggests that the granule cells may be involved in generating the abnormal electrical activity which characterizes this form of epilepsy. We propose to study both the morphological and electrophysiological changes which occur in the dentate gyri of these patients using tissue maintained in the slice preparation. The data obtained from patients with temporal lobe tumors, which do not show the same pattern of granule cell changes, and from rodents. The morphological changes which occur have not been studied at the single cell level, therefore, we will fill single granule cells with intracellular dyes to study both their morphology and projections. In addition, we will inject HRP extracellularly to label groups of cells both involving abnormal electrical discharges. We will attempt, therefore, to determine if the changes underlying the epileptiform activity can be found in the slice using standard intracellular recording techniques, including single electrode voltage clamp. Both the basic membrane properties and the synaptic physiology (both excitatory and inhibitory) will be studied. In addition, we will examine the effects of a number of neuroactive substances, including GABA, glutamate, and biogenic amines, opiate peptides and somatostatin on both rodent and human tissue. These studies will provide important insight into a region of the hippocampus which is affected in temporal lobe epilepsy and which is currently poorly understood.
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