The function of the nervous system depends on the proper connections between individual and groups of nerve cells. Nerve cells communicate with each other and with muscle cells through the release of chemical transmitters at close contact points called synapse. While much is known about the structure of these "synaptic' connections, far less is understood about how these connections adjust to changes by drugs or endogenous chemical substances like hormones. How the communication between nerve cells is changed or "modulated" in both the short and the long term is important to our understanding of the nervous system under normal conditions and those produced by disease. "Neuromodulation" may also be a consideration in the development of new therapeutic approaches. The chemical transmitters used by nerve cells to signal to each other are released from specialized areas called "active zones." The release process is dependent on the movement of calcium into the nerve cell through channels which are clustered at these active zone regions. Since the release of chemical transmitters is dependent on calcium, any modulation of the movement of calcium through its channels can drastically affect the communication between nerve cells and from nerve cells to muscle. This research project will study calcium movement in frog nerves and in specialized cultured cells which may possess nerve-type calcium channels. Unlike other preparations, these may provide direct access to nerve cell calcium channels in order to study neuromodulation. In this way it is possible to understand the factors which control communication in the central and peripheral nervous systems.