Proposal Number: IBN-9511062 Principal Investigator: Ramaswami, Mani The brain is composed of over a billion individual nerve cells connected to one another at complex structures called synapses. Each cell receives input from a multitude of other cells in the brain and may respond by signaling to the cells that receive its outputs. All complex behavior owes itself to signaling by individual nerve cells and the reception of these signals by other nerve and muscle cells. The basic mechanism of signaling by nerve cells is similar in all species. It involves the release of packets of neurotransmitter molecules by the nerve cell. Because the total number of packets available at any time to the nerve cell is very limited, they need to be rapidly replenished for sustained neural function. A model is available which contains a genetic defect in a protein called dynamin which iq unable to replenish these packets. Dynamin is highly conserved across species. Dr. Ramaswami will examine the role of dynamin in neuromuscular communication using specialized genetic methods available, and by novel microscopic techniques. In this model synapses will be altered in a controlled way using modern genetic techniques and behavioral indices will be monitored. In addition, using microscopic methods, the localization of dynamin will be investigated and how it is involved in normal neuronal function. Examination of the role of dynamin at the neuromuscular junction is a fundamental issue that will reveal unique information about synapse function. There is also great relevance of these studies to understanding neuromuscular disorders associated with aberrant signaling between cells.
