Functional interaction of synapsin and Rab3a in the presynaptic vesicle cycle

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Numerous neurological disorders result from disruptions in the communication between nerve cells. Neurons communicate by releasing neuronal transmitters from nerve endings. Impaired transmitter release may produce certain forms of epilepsy. Transmitter molecules are packed into synaptic vesicles, and the preparation of vesicles for release is regulated by numerous proteins. Synapsin is the most abundant synaptic vesicle protein, and its deficiency causes epileptic seizures. Past work shows elimination of another vesicle protein, Rab3a, rescues epilepsy caused by synapsin deletion. This project will investigate how these two proteins interact within nerve endings. To do this, genetically engineered mice that lack synapsin, Rab3a, or both proteins, will be studied. High resolution microscopy to observe vesicle dynamics, and electrical recording will be performed to monitor neuronal activity. In addition, a computational model of the nerve ending will be developed to test whether hypotheses of the protein interaction correctly predict how synapsin and Rab3a affect the release of transmitters. The results of our study will elucidate the mechanisms of synapsin-dependent epilepsy and will suggest new strategies for its treatment. The Universidad Central del Caribe (UCC) is a Hispanic serving institution which strives to provide Puerto Rican students with first-rate education and scientific training. The present project creates a foundation for an excellent training program. The experiments will be performed by graduate, undergraduate, and medical students, and thus the project will provide a support for the students' careers. The project involves collaboration between the UCC and the Wayne State University, and this creates advantageous opportunities for Puerto Rico students to have a practice in a research intense institution. Thus, this project will integrate research and training, advance careers of Puerto Rico students, and help to promote workforce diversity.