This program comprises a series of projects concerned with long-term changes associated with neurotransmitter receptors. Neurotransmitter receptors serve a primary function of modulating conductance changes when bound by their specific neurotransmitter. It is, however, also clear that receptors mediate a large number of longer-term changes in the cell that they are located on. These more lasting effects are of critical importance in the regulation of nerve cell function. For example, receptor number, functional characteristics, and distribution are all regulated by synaptic activity through long-term changes. The goal of our program is to learn more about the sorts of long-term changes that receptors undergo themselves and that they induce in the cell machinery around them. Half of the projects (Bridgman, Cohen, Lichtman) focus in on the most accessible and best understood neurotransmitter receptor - the nicotinic acetylcholine receptor at the neuromuscular junction. Two projects (Krause, O'Malley) concern the molecular sequelae of receptor activation. These studies address the second messenger and signal transduction pathways in two important central nervous system receptors (substance P and dopamine receptors). Finally, one project (Daw) will examine the role of postsynaptic receptors in long-term changes in an intact animal by studying the relation of the NMDA receptor to experience inducible changes in synaptic connectivity in the visual system. By recruiting individuals who work on a wide variety of preparations with a wide range of techniques, but have a common interest in the same general problem, we believe we have a unique opportunity to address some fundamental questions about long-term changes associated with neurotransmitter receptors.
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