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We study the physiology, pharmacology, and biophysics of neurotransmitter receptors with a special emphasis on the function of nicotinic acetylcholine receptors in the brain. These are the receptors which mediate the effects of nicotine on human behavior. We study how these neuronal nicotinic acetylcholine receptors function as ligand-gated ion channels, identifying parts of the molecule which are involved with the binding of neurotransmitter and the conformational change associated with receptor activation. We are also characterizing the selectivity of experimental nicotinic agonists for specific receptor subtypes in the brain. With this understanding we hope to identify the mechanisms through which nicotine-like substances may alleviate some of the learning and memory impairments in animal models of dementia. The ongoing clinical development of new experimental drugs may lead to novel therapeutics for the treatment of Alzheimer’s disease.
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