MORPHOLOGY AND FUNCTION OF THE BASAL GANGLIA

这个项目的总体目标是继续我们的调查 使用各种技术和方法研究基底神经节的功能 由密切联系的首席调查员团队进行的准备工作(工作 一起超过10年)代表了形态学领域， 电生理学、药理学和分子生物学。人与动物 研究表明，帕金森氏症(PK)是由大脑皮质退行性变引起的 黑质纹状体多巴胺能神经元。在PK患者和灵长类动物模型中 在PK中，苍白球和丘脑下层神经元的电活动是 不正常。它们在扣球过程中表现出同步的、有节奏的振荡。它 已经假设他的异常活动是导致 帕金森病(PD)患者的运动症状 手术干预作为消除运动障碍的治疗方法 症状。在这次续签申请中，我们将我们的项目减少到 从原来的四个六个人中奉献出我们的努力去了解 基底节区神经元活动变化的潜在机制 多巴胺失神经引起的神经节。双核(管理 和中央设施)将由调查人员合作共享 有效和高效地使用行政人员、空间和 设备。 我们计划研究振荡和同步的出现 多巴胺失神经大脑中的活动：项目(细胞和 神经元节律性和同步性的分子决定因素)-TO 确定与GP/EP有关的细胞/分子决定因素 急性分离准备中的神经元；投射(同步 苍白球的节律性活动)--电膜、突触和 在切片和体内影响GP/EP的形态决定因素 准备；项目(丘脑底核的节律形成)- 短暂性肾炎的电膜和形态决定因素 切片准备中的神经元；以及投射(节律性和同步性 帕利多-丘脑递归反馈环)--以表征 GP和STN神经元之间的突触相互作用决定因素 节律性振荡和多巴胺在此现象中的作用 器官型培养制剂。

The overall goal of this program project is to continue our investigation of the function of the basal ganglia using a variety of techniques and preparations by a closely linked team of principal investigators (working together for more than 10 years) representing the fields of morphology, electrophysiology, pharmacology, and molecular biology. Human and animal studies have shown that parkinsonism (PK) results from degeneration of the nigrostriatal dopaminergic neurons. In PK patients and in primate models of PK, electrical activity of globus pallidus and sub-thalamic neurons is abnormal. They exhibit synchronous, rhythmic oscillations in spiking. It has been hypothesized that his abnormal activity is responsible for the motor symptoms in Parkinson's disease (PD) and serve as the rational for surgical intervention as a treatment for elimination of the motor symptoms. In this renewal application, we have reduced our projects to four from the original six to dedicate our effort to understand the underlying mechanisms for the changes in neuronal activities in the basal ganglia brought about by dopamine denervation. Two cores (administrative and central facilities) will be cooperatively shared by investigators for the effective and efficient use of administrative staff, space and equipment. We plan to investigate the emergence of oscillatory and synchronous activity in the dopamine denervated brain in: Project (Cellular and Molecular Determinants of Neuronal Rhythmicity and Synchrony)- to characterize the cellular/molecular determinants responsible in GP/EP neurons in acutely isolated preparation; Project (The Synchronized Rhythmic Activity of the Pallidum)-electrical membrane, synaptic and morphological determinants responsible in GP/EP in slice and in vivo preparation; Project (Rhythmogenesis in the Subthalamic Nucleus)- electrical membrane and morphological determinants responsible in STN neurons in slice preparation; and Project (Rhythmicity and Synchrony in the Pallido-Subthalamic Recurrent Feedback Loop)-to characterize the synaptic interactive determinants between GP and STN neurons responsible for rhythmic oscillation and the role of dopamine for this phenomena in organotypic cultured preparation.