The overall goal of this proposal is to understand the neural regulation of certain inhibitory events in the brain, in the belief that this approach will lead to methods that therapeutically enhance neuronal inhibition, and that therefore suppress the abnormal neuronal discharges of epilepsy. To this end, intracellular recording methods will be applied to an in vitro model of mammalian cerebral cortex: the hippocampal slice. The specific focus of this proposal is upon a slow inhibitory event that follows synaptic stimulation of neurons of hippocampus, and probably neurons in many other brain regions as well. We have found that this event is not due to GABAA receptors that are coupled to chloride channels, as is the better understood 'early' inhibitory postsynaptic potential. Instead, it is insensitive to the action of GABAA antagonists, and depends upon an increased membrane conductance to potassium, rather than chloride.
The specific aims of this proposal are 1) to characterize the extent to which transmembrane voltage regulates this late hyperpolarization, 2) to test the hypothesis that increases or decreases in cyclic AMP modulate or control the late hyperpolarization, and 3) to identify transmitter candidates that serve as either the transmitters for, or modulators of, this response.
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