Temporal lobe epilepsy is the most common form of epilepsy in adults and one of the most difficult types to treat. My long-range research goal is to understand the mechanisms of temporal lobe epilepsy so that more effective treatments and preventative strategies can be developed. It has been proposed that the loss of hilar somatostatin-immunoreactive interneurons in the dentate gyrus reduces inhibition of granule cells, lowers seizure threshold, and underlies temporal lobe epilepsy. Recent results from my laboratory provide new support for this mechanism and suggest experimental approaches that will be effective in testing it.
The specific aims and research design of this proposal are to control and compare epileptic kainate-induced rats to: 1) Define the complete axon arbors and synaptic connections of individual hilar somatostatin-immunoreacitve interneurons. In vivo intracellular biocytin labeling will be used with light and electron microscopy to measure the size, distribution, and synaptic density of axon arbors of individual hilar somatostatin-immunoreacitve interneurons and to identify their postsynaptic targets. 2) Determine whether there is reduced inhibition of granule cells in the temporal pole of the hippocampus, the region where hilar somatostatin-immunoreacitve interneuron loss is most severe. The hippocampal slice preparation will be used with dentate gyrus field potential recording, sharp microelectrode recording of poly-and monosynaptic inhibitory postsynaptic potentials in granule cells, and whole-cell voltage-clamp recording of spontaneous and miniature inhibitory postsynaptic currents in granule cells. Adjacent slices will be stained to measure the extent of hilar somatostatin-immunurecative interneuron loss and to correlate that cell loss with measures of functional inhibition. The proposed experiments will provide new data on hilar somatostatin-immunoreactive interneurons in the dentate gyrus and how they change in epileptic animals, test a hypothesis of temporal lobe epileptogenesis, and contribute to a better understanding of the role of somatostatin-immunoreacitve interneurons in temporal lobe epilepsy.
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