NEURONAL ACETYLCHOLINE RECEPTOR MECHANISMS

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Communication in the nervous system takes place by transmission of signals at synapses. Rules governing the function and regulation of synapses and neurotransmitter receptors will be important in understanding higher brain functions. Neuronal nicotinic acetylcholine receptors (AChRs) mediate synaptic transmission throughout the nervous system, but remain poorly characterized. Chick ciliary ganglion neurons provide a useful system for studying neuronal AChRs. The neurons display small and large conductance AChR subtypes throughout development, and recent cDNA cloning strategies have uncovered genes encoding alpha and beta AChR subunits in the ganglion. Studies funded by the previous grant concentrated on the function, development and regulation of AChRs on the neurons. The present renewal will build on those earlier studies. Experiments utilizing the Xenopus oocyte expression system will examine the molecular basis underlying functional AChR subtypes in the ganglion. The expression studies will focus on comparing AChR properties seen in the native ciliary ganglion neurons, with AChRs expressed in frog oocytes following the injection of ganglionic mRNAs coding for AChR subunits. A second major direction will be to explore the mechanisms controlling the regulation of AChRs and synapses on ciliary ganglion neurons during development, and in response to activation of a cyclic AMP second messenger system. The neuronal experiments will provide new insights into the ways receptors and synapses can be modified by cell-cell interactions.