Metabotropic Receptors in Globus Pallidus

苍白球中的代谢型受体

• 批准号: 6698054
• 负责人: OLGA POISIK
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-14 至 2005-12-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6698054
• 关键词: Metabotropic; Receptors; Globus; Pallidus

DESCRIPTION (provided by applicant): The primary objective of this project is to understand how metabotropic glutamate receptors (mGluRs) shape the output of the globus pallidus (GP), an intrinsic component of the basal ganglia, a group of subcortical nuclei that control motor behavior and also have cognitive functions. The activity of the GP is disrupted in some disorders of the basal ganglia such as Parkinson's disease, Hungtington's chorea, and depression. Activation of mGluRs results in important and long-lasting effects in many brain regions, which makes them attractive pharmacological targets in treating neurological disorders. The ultimate goal of this proposal is to collect the necessary information that is required to establish whether mGluRs in the GP can serve as therapeutic targets in treatment or management of neurological diseases that affect the GP output. More specifically, this work will examine the roles of mGluRs on: 1) the excitability of GP neurons, 2) the inhibitory synaptic transmission in the GP, and 3) on the desensitization mechanisms of some postsynaptic mGluRs in the GP. The functional roles of mGluRs and their desensitization mechanisms will be studied using in vitro electrophysiological recordings in living rat brain slices. Commercially available agonists and antagonists to all groups of mGluRs will be utilized. We intend to study the desensitization mechanisms of mGluRs in the GP because some of these receptors are known to desensitize, which limits their usefulness as therapeutic targets in treatment or management of diseased states. Overall, this work will disclose the functions of mGluRs in the GP and their useful potential in treating basal ganglia disorders.

描述(申请人提供)：这个项目的主要目标是了解代谢性谷氨酸受体(MGluRs)如何影响苍白球(GP)的输出，苍白球是基底节的一个内在组成部分，是一组控制运动行为并具有认知功能的皮质下核团。在基底节的一些疾病中，如帕金森氏病、洪廷顿舞蹈症和抑郁症，GP的活动被扰乱。MGluRs的激活在许多脑区产生了重要而持久的影响，这使它们成为治疗神经疾病的有吸引力的药理靶点。这项建议的最终目标是收集必要的信息，以确定GP中的mGluRs是否可以作为影响GP产量的神经疾病的治疗靶点。更具体地说，本工作将研究mGluRs在以下方面的作用：1)GP神经元的兴奋性，2)GP中的抑制性突触传递，3)GP中一些突触后mGluRs的脱敏机制。MGluRs的功能作用及其脱敏机制将利用体外电生理记录在活体大鼠脑片上进行研究。将使用所有mGluR组的商业上可用的激动剂和拮抗剂。我们打算研究mGluRs在GP中的脱敏机制，因为已知其中一些受体具有脱敏作用，这限制了它们在疾病状态治疗或管理中作为治疗靶点的有效性。总体而言，这项工作将揭示mGluRs在GP中的功能及其在治疗基底节疾病方面的有用潜力。