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To understand the pathophysiological mechanisms underlying the neurological disorders in myosin Va diseases, we conducted an integrated analysis at the molecular, cellular, electrophysiological, and behavioral levels using the<jats:italic>dilute-neurological<\/jats:italic>(<jats:italic>d-n<\/jats:italic>) mouse mutant. These mice manifest an ataxic gait and clonic seizures during postnatal development, but the neurological disorders are ameliorated in adulthood. We found that smooth endoplasmic reticulum (SER) rarely extended into the dendritic spines of Purkinje cells (PCs) of young<jats:italic>d-n<\/jats:italic>mice, and there were few, if any, IP<jats:sub>3<\/jats:sub>receptors. Moreover, long-term depression (LTD) at parallel fiber\u2013PC synapses was abolished, consistent with our previous observations in juvenile lethal<jats:italic>dilute<\/jats:italic>mutants. Young<jats:italic>d-n<\/jats:italic>mice exhibited severe impairment of cerebellum-dependent motor learning. In contrast, adult<jats:italic>d-n<\/jats:italic>mice showed restoration of motor learning and LTD, and these neurological changes were associated with accumulation of SER and IP<jats:sub>3<\/jats:sub>receptors in some PC spines and the expression of myosin Va proteins in the PCs. RNA interference-mediated repression of myosin Va caused a reduction in the number of IP<jats:sub>3<\/jats:sub>receptor-positive spines in cultured PCs. These findings indicate that myosin Va function is critical for subsequent processes in localization of SER and IP<jats:sub>3<\/jats:sub>receptors in PC spines, LTD, and motor learning. Interestingly,<jats:italic>d-n<\/jats:italic>mice had defects of motor coordination from young to adult ages, suggesting that the role of myosin Va in PC spines is not sufficient for motor coordination.<\/jats:p>","DOI":"10.1523\/jneurosci.5651-10.2011","type":"journal-article","created":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T17:03:10Z","timestamp":1303318990000},"page":"6067-6078","source":"Crossref","is-referenced-by-count":34,"title":["A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va 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