The proposed research concerns synaptic transmission, voltage dependent ionic conductances, and the relation between them, in bullfrog sympathetic and rodent hippocampal neurons. The main technique used is voltage clamp. This allows one to separate and in favorable cases quantitate, the various inward and outward currents present. This will allow reconstruction of the totality of the electrical behavior of these cells. Also, the effects of neurotransmitters and of synaptic stimulation on these individual currents can be determined. In turn this enables prediction of the effects of slow synaptic inputs on neuron electrical behavior. The main difference between ganglia and hippocampal neurons is in difficulty of experiment and interpretation. Bullfrog neurons are relatively accessible and robust, and lack complex processes which cause space clamp problems. Hippocampal neurons are less tractable in all 3 aspects, but are more relevant to clinical problems. In both cases fresh and cultured material will be used. The main thrust will be on the muscarinically-controlled outward currents IM and IAHP which have been previously characterized by this laboratory. Because these are novel conductances they are still not thoroughly understood. The mechanisms linking muscarinic receptor to these channels, and the features of the channels themselves, are largely unknown. Various patch clamp techniques will be used to explore this question. This research has relevance to epilepsy and Alzheimer's disease, the former because the data obtained will help explain abnormal neuronal excitability, and the latter because data concerning cortical cholinergic actions will be forthcoming.
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