Morris K. Udall Centers of Excellence for Parkinson's Disease Research at Emory University

项目概要-总体中心 莫里斯K。埃默里大学Udall Parkinson's Disease Center of Excellence for Parkinson's Disease Research 大学是一个合作研究计划，研究帕金森症的病理生理学， 帕金森病（PD）的最佳治疗方法。该中心利用基础设施的经证实的能力， 神经节研究社区在埃默里大学进行合作转化研究。尤德尔中心的其他资产是埃默里的耶基斯国家灵长类动物研究中心的灵长类动物研究， 以及美国最大的运动障碍诊所之一的存在。该中心由四个项目和三个核心组成。这项计划中的研究将揭示大脑皮层中特定的投射神经元群的帕金森病相关活动变化，这些活动变化反过来将 帮助我们更好地了解帕金森症的病理生理学，并优化治疗策略。项目1（由Jaeger博士领导）将利用啮齿动物实验进行大规模电压成像和脑切片记录，并使用神经计算方法开发帕金森症皮质功能障碍的机制模型。项目2（Galvan博士），将探索皮质纹状体和皮质纹状体的自发和任务相关活动， 在正常和正常的初级运动皮层（M1）和辅助运动区（SMA）的皮质脊髓神经元， 帕金森病猴子，使用光标记方法来识别记录的神经元的投射目标。项目3（史密斯博士）将检查M1和SMA微电路的形态学变化以及灵长类动物皮层投射神经元连接体中帕金森病相关变化，这是一个几乎未探索的主题，与项目1和2中的数据解释高度相关。临床“催化剂”项目4是在反应抑制任务中检查帕金森病相关的皮层活动变化，研究 PD患者的皮质电图和脑电图信号。功能实验 还将研究左旋多巴和脑深部电刺激治疗在这些范例中的作用。所有项目 将由一个行政核心（核心A，Wichmann博士，PI; Smith博士，副主任，Ms Holbrook，管理员），以及一个服务核心，为项目1和2提供解剖服务，为项目2和3提供行为评估，为所有项目提供统计服务（核心B，Galvan博士）。临床 核心（核心C）将支持项目4，为人类研究提供招募和后勤服务。除了 为了实现其研究使命（目标1），中心将帮助年轻科学家发展他们在帕金森病研究方面的职业生涯（目标2），并将从事广泛的外联工作，旨在宣传中心（和Udall 中心网络）向公众公布研究结果（目标3），覆盖所有年龄组和背景水平。一部分 在外联议程中，中心计划为病人及其护理人员组织年度外联活动。 慷慨的内部支助资金将帮助中心资助其一些教育和外展任务， 以及其试点赠款计划，旨在扩大在埃默里PD研究。

Project Summary – Overall Center The Morris K. Udall Parkinson's Disease Center of Excellence for Parkinson’s Disease Research at Emory University is a collaborative research program that studies the pathophysiology of parkinsonism with the goal of optimizing the treatment for Parkinson’s disease (PD). The Center draws upon the proven ability of the basal ganglia research community at Emory to conduct collaborative translational research. Other Udall Center assets are the availability of primates for research at the Yerkes National Primate Research Center at Emory, and the presence of one of the largest movement disorders clinic in the US. The Center consists of four projects and three cores. The planned research will shed light on the poorly understood parkinsonism-related activity changes of specifically identified groups of projection neurons in the cerebral cortex which, in turn, will help us to better understand the pathophysiology of parkinsonism, and to optimize therapeutic strategies. Project 1 (led by Dr. Jaeger) will utilize rodent experiments for large-scale voltage imaging and brain slice recordings and use neural computational approaches to develop mechanistic models of cortical dysfunction in parkinsonism. Project 2 (Dr. Galvan), will explore the spontaneous and task-related activity of corticostriatal and corticospinal neurons in the primary motor cortex (M1) and the supplementary motor area (SMA) in normal and parkinsonian monkeys, using an opto-tagging approach to identify the projection targets of the recorded neurons. Project 3 (Dr. Smith) will examine morphological changes in the M1 and SMA microcircuitry and parkinsonism-associated changes in the connectome of cortical projection neurons in primates, a topic that is virtually unexplored and of high relevance to the interpretation of data in projects 1 and 2. The clinical ‘Catalyst’ project 4 is an examination of parkinsonism-related changes in cortical activity in response inhibition tasks, studied in electrocorticography and electroencephalography signals in patients with PD. The functional experiments will also study the effects of levodopa and deep brain stimulation treatments in these paradigms. All projects will be supported by an administrative core (Core A, Dr. Wichmann, PI; Dr. Smith, Associate Director, Ms Holbrook, administrator), and by a service core that provides anatomical services to projects 1 and 2, behavioral assessments to projects 2 and 3, and statistical services to all projects (Core B, Dr. Galvan). A clinical core (Core C) will support project 4 with recruitment and logistic services for the human studies. In addition to pursuing its research mission (aim 1), the Center will help young scientists to develop their career in PD research (aim 2), and will engage in extensive outreach efforts, aimed at communicating the Center’s (and Udall Center network) research findings to the public (aim 3), reaching all age groups and background levels. As part of the outreach agenda, the center plans to organize annual outreach events for patients and their caregivers. Generous internal support funds will help the Center to fund some of its education and outreach missions, as well as its pilot grant program, designed to expand PD research at Emory.