Cerebellar Neuromodulation

描述（由申请人提供）：小脑的主要功能是运动协调和维持平衡。小脑功能障碍，无论是遗传性疾病或后天缺乏的结果，导致不协调的运动（共济失调）。目前还没有治愈任何遗传性共济失调，并有几个有效的治疗选择共济失调一般。然而，在过去的二十年中，已显示多巴胺能激动剂在减轻多种小脑共济失调的症状方面具有治疗有效性。β-肾上腺素能药物的作用机制尚不清楚。鉴于5-羟色胺的治疗效用，重要的是要描绘其在小脑中的作用机制，作为改善其在共济失调中的治疗用途的第一步。本提案的目的是描述多巴胺能药物对小脑浦肯野细胞的影响。特别是，我们将测试的假设，5-羟色胺调节AMPA/红藻氨酸受体在这些神经元的贩运。 公共卫生相关性：小脑的主要功能是运动协调和维持平衡。小脑功能障碍，无论是遗传性疾病或后天缺乏的结果，导致不协调的运动（共济失调）。目前还没有治愈任何遗传性共济失调，并有几个有效的治疗选择共济失调一般。然而，在过去的二十年中，已显示多巴胺能激动剂在减轻多种小脑共济失调的症状方面具有治疗有效性。β-肾上腺素能药物的作用机制尚不清楚。鉴于5-羟色胺的治疗效用，重要的是要描绘其在小脑中的作用机制，作为改善其在共济失调中的治疗用途的第一步。本提案的目的是描述多巴胺能药物对小脑浦肯野细胞的影响。

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.