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。由于遗传障碍或后天缺陷导致的小脑功能障碍会导致运动不协调(共济失调)。目前，任何遗传性共济失调都没有治愈方法，总的来说，几乎没有有效的治疗方案。然而，在过去的二十年里，5-羟色胺能激动剂已经被证明在治疗上有效地减轻了各种各样的小脑性共济失调的症状。5-羟色胺能药物的作用机制尚不清楚。鉴于5-羟色胺的治疗作用，描述它在小脑中的作用机制是改善其在共济失调治疗中的应用的第一步，这一点很重要。这项建议的目的是描绘5-羟色胺能药物对小脑浦肯野细胞的影响。特别是，我们将检验5-羟色胺调节AMPA/海人藻酸受体在这些神经元中运输的假设。

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.