Investigation of Pallidal Neurons in Motor Inhibition

苍白球神经元运动抑制的研究

• 批准号: 10592733
• 负责人: Savio Chan
• 金额: $ 53.63万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2024-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592733
• 关键词: Adult; Animal Model; Award; Axon; Basal Ganglia; Behavioral; Calcium-Binding Proteins; Cell Nucleus; Cells; Chronic; Complex; Corpus striatum structure; Data; Disease; Dissection; Dopamine; Dorsal; Electrophysiology (science); FOXP2 gene; Fiber; Functional disorder; Funding; Genetic; Globus Pallidus; Goals; Health; Intervention; Investigation; Knowledge; Lesion; Midbrain structure; Modeling; Molecular; Motor; Motor Activity; Motor output; Movement; Mus; Neurons; Oxidopamine; Parkinson Disease; Parvalbumins; Pathway interactions; Pattern; Photometry; Play; Process; Property; Regulation; Reporter; Research; Role; Series; Shapes; Signal Transduction; Site; Surveys; Symptoms; Synapses; Taxonomy; Testing; Therapeutic; Translations; base; cell type; dopaminergic neuron; experimental study; improved; in vivo; insight; motor behavior; motor control; optogenetics; patch clamp; phase change; relating to nervous system; tool; transcription factor

Project Summary The long-term goal of this project is to deepen our understanding of how the external globus pallidus (GPe) within the basal ganglia controls movement and how it goes awry in Parkinson’s disease (PD). Despite compelling evidence that the GPe plays a critical role in regulating motor activity, its neuronal composition has been poorly defined. As the neurons that encompass the GPe are heterogeneous, understanding how the activity of the GPe is regulated in behavioral and disease contexts has posed a challenge. Through a series of investigations during the last funding cycle, we surveyed the molecular landscape of the mouse GPe. By characterizing a number of driver and reporter lines, we have now established a near-complete neuron taxonomy of the GPe. Using these newly available genetic tools in conjunction with cell- and circuit-specific approaches, we began to understand how GPe neuron subtypes control full-body movements. Through a combination of in vivo and ex vivo approaches, we will examine the activity dynamics of GPe neuron subtypes and their regulation of their synaptic partners to clarify the mechanisms involved. These experiments will provide new information about how motor inhibition is executed by the GPe and the basal ganglia as a whole. Using a well-established chronic model of PD, we will provide unprecedented insights into how alterations in these processes underlie hypokinetic symptoms of PD. The yielded knowledge will not only inform the processes underlying motor (dys)function but will also help develop circuit interventions that target the hypokinetic symptoms of PD.

项目摘要 本项目的长期目标是加深我们对外部苍白球（GPe） 基底神经节内的神经元控制运动，以及它在帕金森病（PD）中如何出错。尽管 令人信服的证据表明，GPe在调节运动活动中起着关键作用，其神经元组成 定义不好。由于包含GPe的神经元是异质的，因此了解GPe的神经元是如何形成的。 在行为和疾病背景下调节GPe的活性已经提出了挑战。通过一系列 在上一个资助周期的研究中，我们调查了小鼠GPe的分子景观。通过 通过表征一些驱动和报告细胞系，我们现在已经建立了一个接近完整的神经元， GPe的分类。使用这些新的可用的遗传工具结合细胞和电路特异性 通过这种方法，我们开始了解GPe神经元亚型如何控制全身运动。通过 结合体内和体外方法，我们将研究GPe神经元亚型的活动动力学 以及它们对突触伴侣的调节，以阐明所涉及的机制。这些实验将 提供了关于运动抑制是如何由GPe和基底神经节作为一个整体来执行的新信息。 使用一个完善的慢性PD模型，我们将提供前所未有的见解，如何改变 这些过程是PD运动功能减退症状的基础。知识不仅是知识， 处理潜在的运动（dys）功能，但也将有助于开发针对 PD的运动功能减退症状。