Cerebello-Basal Ganglia Interactions

小脑-基底神经节相互作用

基本信息

批准号：
8690186
负责人：
Kamran Khodakhah
金额：
$ 36.17万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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/8690186
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

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

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项目摘要

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多样化的运动障碍，通常以肌肉的长期收缩为特征。最常见的肌张力障碍是特发性。尽管如此，几个基因与肌张力障碍有关。非缺乏性肌张力障碍的最普遍原因是对基底神经节的损害。然而，最近，有证据表明，在某些情况下，小脑功能障碍也可能有助于（甚至煽动）肌张力障碍。我们的工作假设是，异常的小脑活性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。已经在啮齿动物和灵长类动物中描述了通过丘脑的中央外侧核从小脑到基底神经节的直接脱节连接的解剖底物。在此提案中，我们希望检验以下假设：在健康的个体中，这种双不触及的联系允许小脑和基底神经节之间的快速沟通。此外，我们将检验以下假设：这种突触途径提供了主要的导管，在基底神经神经元中，异常的小脑活性会使异常的小脑活性作用，从而导致肌张力障碍。该提案的成功完成将提高我们对小脑和基底神经节之间相互作用的性质的理解，以进行运动协调。此外，它还可以提供一个详细的机械洞察力，以了解异常小脑活性如何促进肌张力障碍。