The role of cerebellar Golgi interneurons in the adaptive timing of movements

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DESCRIPTION (provided by applicant): How the cerebellum implements motor learning is still largely a mystery. Particularly, the mechanism by which it calibrates the timing of movements remains to be elucidated. Whereas most studies of learning have focused on changes in the strength of neural signaling pathways, my work examines the dynamics of neural signaling. Longstanding theories suggest that Golgi cells, a class of inhibitory interneurons, play a critical role in controlling the dynamics of neural signal processing in the cerebellum, thus determining the timing of learned movements. To test this hypothesis, I will take advantage of several recent technical advances: 1) recording of Golgi cells in vivo, which I have been conducting to monitor activity before and after motor learning, to determine whether changes in Golgi cell activity account for changes in movement timing, and 2) transgenic mice in which the Golgi cells can be reversibly inactivated, which I will use to study the consequences of removing Golgi cells from the circuit, and examined the impact at behavioral levels. The old theories and new tools provide me a unique opportunity to investigate the contribution of a particular cell type in the cerebellar circuit to its function in motor learning. In essence, my work will provide insight on how the brain encodes and stores timing information. Motor learning disorders are one of the most common health problems including cerebellar astocytomas, spinocerebellar ataxia, cerebellar hypoplasia, cerebellar agenesis, autism, and others. My belief is that a good understanding of how normal neural networks function and how, in particular, the cerebellum encodes motor learning will provide the basis for developing rational therapeutic treatments for people suffering from motor learning disorders.