This project is concerned with the basic physiological processes responsible for regulating the amount of transmitter released presynaptically by a nerve impulse, and the postsynaptic processes responsible for mediating long-lasting inhibition. Experiments will be performed on the giant synapse of the squid to characterize in detail interactions between residual intracellular calcium following nervous activity and calcium channels that might contribute to synaptic facilitation, a form of synaptic plasticity. Voltage-clamp measurements and photochemical detection of presynaptic calcium will be used to determie the role of calcium diffusion in regulating internal calcium levels near transmitter release sites, the mechanism by which elevated sodium leads to long-lasting synaptic potentiation, another form of synaptic plasticity, the effect of membrane potential on calcium-evoked transmitter release, and the spatial distribution of presynaptic calcium channels. Other experiments will be performed on central neurons in Aplysia to determine the factors responsible for inhibition of long duration, a long-lasting form of synaptic inhibition. The role of intracellular calcium as a possible second messenger in this synaptic response will be determined, and the possible mediation of calcium action by a calmodulin receptor and membrane-bound protein kinases will be explored. The significance of these experiments lies in the central roles that synaptic plasticity and long-lasting inhibition play in the modulation of adaptive behaviors by experience. The information sought is also fundamental to an understanding of the information processing capabilities of nervous systems.
Showing the most recent 10 out of 48 publications
