Different modes of glutamate release at PF-SC synapses in the cerebellum

Oregon Health & Science University, Portland OR

Investigators

Abstract

DESCRIPTION (provided by applicant): The cerebellum is primarily responsible for coordinating motor movement by processing and modifying descending motor commands from the cortex. General cerebellar circuitry is rather homogenous; however, considerable heterogeneity exists at distinct synaptic connections within this microcircuitry. Preliminary studies suggest there is more variability in the regulation of glutamate release at individual parallel fiber terminals than originally reported. The goal of this proposal is to better understan signaling properties of the parallel fibers through a careful study of individual parallel fiber - stellate cell synapses. Aim 1 will investigate the source of glutamate responsible for activation o extrasynaptic NMDA receptors on the stellate cells. This work will identify whether action potential-dependent, synchronous release or action potential-independent, asynchronous release is the primary method of glutamate release required to elicit NMDA receptor currents. Using 2-photon laser uncaging of glutamate, Aim 2 will determine the extent of NMDAR activation by mimicking asynchronous and multivesicular release. This Aim will also establish whether the NMDARs are localized perisynaptically or dispersed evenly throughout the stellate cell dendritic tree. Through a clearer understanding of cerebellar microcircuitry, we may potentially identify new therapeutic strategies for the treatment of cerebellar specific motor deficits.