The goal of these experiments is to better understand the sequence of steps that generate and remove synapses. The approach will be to use a series of transgenics mice that express various fluorescent proteins in some or all of their axons that project to muscle fibers. By using these mice with previously developed techniques that permit monitoring synapses over time in living animals, we will follow the vents that lead to the localization of synapses to a small synaptic site that contains a high density of neurotransmitter receptors. We will also attempt to understand how and why multiple axons come to converge on a signal site and what mechanisms lead to the withdrawal of all but one axon. Because different axons converging on the same muscle an expressing different colors of fluorescent proteins, we will be able to monitor over time, the competitive interactions between axons with far greater resolution than before. In addition, because we can photoconvert one fluorescently labeled axon at a junction contacted by two inputs and reconstruct in the electron microscope the fine structure of each of the competitors, we can visualize the changes that take place with greater spatial resolution than previously. Lastly, by using these approaches in mice that lack wither the post- synaptic machinery to generate synapses, or the presynaptic machinery to release neurotransmitter, we will be able to study the effects of activity and post-synaptic differentiation factors on the formation and elimination of synapses. Understanding the rules that govern formation and elimination of synapses are likely to be fundamental to understanding the mechanisms by which humans learn and remember.
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