The innumerable cells in the brain form countless numbers of connections (synapses) with each other. These synapses act as gatekeepers for the transmission of electrical signals through neural circuits, which underlie behavior. Recent studies have focused on mechanisms that maintain constant synaptic function (synaptic homeostasis) throughout an animal's life; these mechanisms are essential for maintaining the normal function of the brain. The proposed research will examine the induction and expression of synaptic homeostasis. Our preliminary findings provide the first direct evidence that intracellular calcium triggers synaptic homeostasis; the role of calcium will be further explored in this research. In addition, we have identified a membrane channel activated by calcium that appears to be important in the expression of synaptic homeostasis. The proposed experiments will further define the properties of this novel mechanism and its role in synaptic homeostasis. These studies will utilize transgenic techniques, imaging of fluorescent indicators, biochemistry, and electrophysiology. Experiments will be performed using the Drosophila larval neuromuscular junction, which is one of the preferred model systems for synaptic studies since these synapses are identifiable, accessible and amenable to genetic manipulations. The findings of this basic research will advance our knowledge of synaptic homeostasis and should be applicable to the nervous systems of all animals including humans. These results will be widely disseminated through attendance at international meetings and publications in international journals. The research projects will involve undergraduate students including underrepresented minority students; this will provide an entry point for these students to pursue careers in scientific research and teaching. In addition, the proposal will fund the research of graduate students pursuing advanced degrees in the Biological Sciences. Finally, the theory and results of this research will be communicated to students in two Neuroscience lecture courses and the experimental techniques are incorporated in a Neuroscience laboratory course.
