The objective of this proposal is to understand the dendritic mechanisms that underlie normal and seizure states of the brain. In order to attain this objective, it is first necessary to analyze the multiple factors (e.g., synaptic and non-synaptic membrane conductances) that interact to influence neuronal excitability. Because the hippocampus is involved in important forms of abnormal discharges, both generalized and focal epilepsy, the electrical responses of hippocampal neurons will be studied using intracellular volatge recordings in the slice preparation. Very little is known about dendritic electrical properties and how they are involved in epileptic seizure discharges, although the central role of dendrites in neuronal excitability is well accepted. Therefore, it is the primary aim of this proposal to systematically analyze the non-synaptic ion specific conductances of dendrites. For this purpose we will use a novel preparation involving intradendritic recordings from physically isolated dendrites in the hippocampus. This preparation will allow more precise analysis of dendritic electrical events than previous conventional recordings from the cell body. In conjunction with this study, I will use specific channel blocking agents to test the hypothesis that potassium-dependent properties of the dendrite play a crucial role in controlling neuronal discharge. I will further test the hypothesis that convulsant and clinically relevant anticonvulsant agents have their effects by acting primarily on these dendritic properties. These studies therefore are important for a complete understanding of dendritic function in neuronal excitability.
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