Cerebello-Basal Ganglia Interactions

小脑-基底神经节相互作用

• 批准号: 8541900
• 负责人: Kamran Khodakhah
• 金额: $ 35.25万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541900
• 关键词: Basal Ganglia; Cell Nucleus; Cells; Cerebellar Diseases; Cerebellum; Communication; Corpus striatum structure; Dystonia; Dystonia 12; Fire - disasters; Functional disorder; Genes; Individual; Modeling; Motor; Movement Disorders; Mus; Muscle Contraction; Na(+)-K(+)-Exchanging ATPase; Nature; Neurons; Output; Parkinson Disease; Pathologic; Pathway interactions; Physiological; Primates; Protein Isoforms; Rodent; Testing; Thalamic structure; Therapeutic Intervention; Tremor; Work; design; in vivo; insight; loss of function mutation; mouse model

DESCRIPTION (provided by applicant): Dystonias comprise a diverse group of movement disorders that are often characterized by prolonged contraction of muscles. The most common dystonias are idiopathic. Nonetheless, several genes have been implicated in dystonia. The most prevalent cause of nonidiopathic dystonia is damage to the basal ganglia. Recently, however, evidence has amassed in support of the notion that in some cases cerebellar dysfunction may also contribute to (or even instigate) dystonia. Our working hypothesis is that aberrant cerebellar activity dynamically alters the physiologic function of the basal ganglia thus resulting in dystonia. An anatomical substrate for a direct disynaptic connection from the cerebellum to the basal ganglia via the centrolateral nucleus of the thalamus has been described both in rodents and primates. In this proposal we wish to test the hypothesis that in healthy individuals this disynaptic connection allows for rapid communication between the cerebellum and the basal ganglia. Further, we will test the hypothesis that this disynaptic pathway provides the primary conduit through which aberrant cerebellar activity forces erratic burst firing in the basal ganglia neurons thereby causing dystonia. Successful completion of this proposal will advance our understanding of the nature of interactions between the cerebellum and basal ganglia for motor coordination. Additionally, it may also provide a detailed mechanistic insight as to how aberrant cerebellar activity instigates dystonia.

描述（由申请人提供）：肌张力障碍包括一组不同的运动障碍，其特征通常是肌肉收缩延长。最常见的肌张力障碍是特发性的。尽管如此，有几个基因与肌张力障碍有关。非特发性肌张力障碍最常见的原因是基底神经节损伤。然而，最近有越来越多的证据支持这一观点，即在某些情况下，小脑功能障碍也可能导致（甚至诱发）肌张力障碍。我们的工作假设是异常的小脑活动动态地改变了基底神经节的生理功能，从而导致肌张力障碍。啮齿动物和灵长类动物都描述了通过丘脑中央外侧核从小脑到基底神经节直接双突触连接的解剖学基底。在这个建议中，我们希望测试的假设，在健康的人，这种双突触连接允许小脑和基底神经节之间的快速通信。此外，我们将检验这样的假设：这种反突触通路提供了主要渠道，异常的小脑活动通过该渠道迫使基底神经节神经元不稳定的爆发性放电，从而导致肌张力障碍。成功地完成这一建议将促进我们的理解之间的相互作用的性质小脑和基底神经节的运动协调。此外，它也可以提供一个详细的机制，了解异常小脑活动如何煽动肌张力障碍。