9514266 Ross The central nervous system often appears like a dense, bewildering array of neurons and of neuronal synaptic interactions. Part of the problem is that the functional significance of specific locations at which synapses occur on cells is largely unknown. The focus of research funded by this grant is on determining the significance of the spatial arrangement of synapses on Purkinje cells, which are the largest neurons in the cerebellum and which provide the only output to other parts of the brain. This focus relates to the complex problem of how voltage-dependent membrane conductances in Purkinje cell input regions, the dendrites, and the architecture of these neurons influence the integration process. Experiments are designed to determine the functional significance of the spatial patterns of these synaptic inputs. The primary technique is optical recording of calcium concentrations through the use of indicator dyes in slices of brain tissue. Calcium concentrations, when combined with an electrical recording, are good indicators of changes in intracellular potentials throughout neurons and hence of local neuronal activity. The relatively stereotyped circuitry of the cerebellar cortex provides a favorable model system for studying the functional significance of cell geometry and synaptic interactions in detail. These studies should provide much needed, detailed descriptions of synaptic interactions in critically important cerebellar neurons. Such descriptions will greatly enhance knowledge of information processing in mammalian neurons at the single cell level.
