Metabotropic Receptors in Globus Pallidus

描述（由申请人提供）：本项目的主要目的是了解代谢型谷氨酸受体（mGluRs）如何塑造苍白球（GP）的输出，苍白球是基底神经节的内在成分，是一组控制运动行为并具有认知功能的皮质下核团。GP的活性在基底神经节的一些疾病中被破坏，例如帕金森病、亨廷顿舞蹈病和抑郁症。mGluRs的激活在许多脑区域中产生重要且持久的作用，这使得它们在治疗神经系统疾病中成为有吸引力的药理学靶点。该提案的最终目标是收集必要的信息，以确定GP中的mGluRs是否可以作为治疗或管理影响GP输出的神经系统疾病的治疗靶点。更具体地说，这项工作将检查mGluRs的作用：1）GP神经元的兴奋性，2）抑制性突触传递的GP，和3）在GP的一些突触后mGluRs的脱敏机制。mGluRs的功能作用及其脱敏机制将使用活体大鼠脑切片的体外电生理记录进行研究。将使用所有mGluR组的市售激动剂和拮抗剂。我们打算研究mGluRs在GP中的脱敏机制，因为已知这些受体中的一些会脱敏，这限制了它们作为治疗或管理疾病状态的治疗靶点的有用性。总之，这项工作将揭示的功能mGluRs在GP和他们的有用的潜力，在治疗基底神经节疾病。

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.