Maintenance and Plasticity at the Frog Neuromuscular Junction

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IBN 9602136 PI: Elizabeth A. Connor Neurons communicate with their target cells at specialized points of contact called synapses. The coordinated maintenance of the synapse between a neuron and its target is necessary to ensure reliable communication between these cells and the normal functioning of the nervous system. Though some synapses between neurons and their targets persist throughout the entire life of an animal, the mechanism by which neurons are maintained at synaptic sites is not understood. The goal of this proposal is to identify factors that contribute to the stability of neurons at synapses using the frog neuromuscular junction as a model. At the frog neuromuscular junction, a motor neuron forms a synapse with a target muscle cell. The frog neuromuscular junction is a powerful system in which to study synapse stability since neurons can be studied in the absence of target muscle to reveal nonmuscle stabilization interactions normally masked in the presence of target. Further, the stability of target-deprived neurons can be manipulated to test for stabilization factors. The role of a glial support cell, the terminal Schwann cell, in the stability and maintenance of the neuron will be determined by assessing the stability of neurons after removal of terminal Schwann cells from identified synaptic sites. The ability of a neurotrophic factor produced by Schwann cells to rescue and stabilize neurons will be tested. The role of connective tissue molecules found at or near synaptic sites in the stabilization of neurons will also be determined. These experiments will yield new information on the mechanisms that stabilize and maintain neurons at synaptic sites and will expand our understanding of the molecular and cellular interactions that govern synaptic plasticity.