This application makes use of state-of-the-art imaging techniques to spatially and temporally resolve the propagation of specific ionic transients. Dr. Ross will investigate this problem by using a relatively noninvasive high speed imaging system which can examine all parts of the cell simultaneously, This optical technique can give information about specific ion concentration changes and voltage changes. The signals can be interpreted in terms of the spatial distribution and propagation of dendritic events and the distribution of specific membrane channels. Dr. Ross will inject individual Purkinje cells in cerebellar slices with fluorescent ion indicators and high speed images, correlated with simultaneous electrical measurements made under various conditions. The special imaging technology will be specifically used for measuring intracellular calcium and sodium concentration transients in fine dendritic processes. These experiments will attempt to define those factors (intrinsic membrane conductances, synaptic interactions, and neuromodulators) which influence the generation of local intracellular calcium changes and the propagation of regenerative potentials. Because it is essential to have information about the way synaptic inputs are integrated and processed in a neuron results from this study will ultimately help to better understand the cellular mechanisms of learning and memory.***