Cerebellar Neuromodulation

描述（申请人提供）：小脑的一个主要功能是运动协调和维持平衡。小脑功能障碍，无论是遗传性疾病还是后天缺陷的结果，导致不协调的运动（共济失调）。目前还没有治愈遗传性共济失调的方法，一般来说，对共济失调也没有什么有效的治疗选择。然而，在过去的二十年中，血清素能激动剂已被证明在治疗上有效地减轻各种小脑共济失调的症状。5 -羟色胺类药物的作用机制尚不清楚。鉴于5 -羟色胺的治疗效用，重要的是描述其在小脑中的作用机制，作为改善其治疗共济失调的第一步。该建议的目的是描述血清素能药物对小脑浦肯野细胞的影响。特别是，我们将测试5 -羟色胺调节这些神经元中AMPA/Kainate受体的运输的假设。

DESCRIPTION (provided by applicant): A major function of the cerebellum is motor coordination and maintenance of balance. Dysfunction of the cerebellum, either as a consequence of a hereditary disorder or acquired deficiency, results in uncoordinated movement (ataxia). There is presently no cure for any of the hereditary ataxias, and there are few effective therapeutic options for ataxia in general. However, during the last two decades serotonergic agonists have been shown to be therapeutically effective in reducing the symptoms of a wide variety of cerebellar ataxias. The mechanism of action of serotonergic drugs is not understood. Given the therapeutic utility of serotonin it is important to delineate its mechanism of action in the cerebellum as a first step towards improving its therapeutic use in ataxia. The goal of this proposal is to delineate the effects of serotonergic drugs on cerebellar Purkinje cells. In particular, we will test the hypothesis that serotonin regulates the trafficking of AMPA/Kainate receptors in these neurons. PUBLIC HEALTH RELEVANCE: A major function of the cerebellum is motor coordination and maintenance of balance. Dysfunction of the cerebellum, either as a consequence of a hereditary disorder or acquired deficiency, results in uncoordinated movement (ataxia). There is presently no cure for any of the hereditary ataxias, and there are few effective therapeutic options for ataxia in general. However, during the last two decades serotonergic agonists have been shown to be therapeutically effective in reducing the symptoms of a wide variety of cerebellar ataxias. The mechanism of action of serotonergic drugs is not understood. Given the therapeutic utility of serotonin it is important to delineate its mechanism of action in the cerebellum as a first step towards improving its therapeutic use in ataxia. The goal of this proposal is to delineate the effects of serotonergic drugs on cerebellar Purkinje cells.