Integration of synaptic excitation and inhibition in the deep cerebellar nuclei



 DESCRIPTION (provided by applicant): Neurons of the cerebellar nuclei (CbN), which are the main output of the cerebellum and involved in motor coordination, integrate inhibition from Purkinje (Pkj) cells of the cerebellar cortex and excitation from mossy fibers and inferior olive. Dysfunction of CbN cells contributes to motor diseases like ataxia and dystonia. Recent work showed that synchrony of Pkj simple spikes inhibits spontaneous firing by CbN cells during brief IPSPs, but permits short-latency spiking after IPSPs; this periodic inhibition/disinhibition lets CbN cells phase- lock their firing to that of synchronized Pkj cells. In this proposal, the present experiments are designed to investigate how mossy-fiber-driven synaptic excitation modulates CbN cell responses to inhibition. Whole-cell recordings will be made from large projection CbN cells in P17-P23 mouse cerebellar slices at 34-37°C in GABAA receptor antagonists to block endogenous inhibition. Inhibitory synaptic conductances from Pkj cells will be applied by dynamic clamp and synaptic excitation from mossy fibers will be activated by electrical stimulation. Different patterns and amounts of excitation and inhibition will be applied and CbN cell firing responses during synaptic integration will be examined. These data will provide insights into mechanisms of information encoding in the cerebellum.