Metabotropic Receptors in Globus Pallidus

18.我在这个研究项目下的目标是研究大鼠苍白球中代谢型谷氨酸受体的功能，并确定这些受体如何调节这一脑区的活动。苍白球的输出在中枢神经系统的许多疾病中被破坏，本研究的最终目标是确定代谢型谷氨酸受体是否可以成功地用作治疗或管理这些疾病状态的治疗靶点。在此奖学金下，我打算提高和拓宽我在电生理学和免疫细胞化学方面的技能。在我的赞助商的指导下，我希望在我计划实验，批判性地分析和解释数据，并揭示我的结果的意义的能力方面取得进展。与此同时，我将参加科学会议和研讨会，我计划在那里介绍和讨论我的发现，这将有助于我与其他科学家交流的能力。这些技能的发展将是必不可少的，在我未来的职业生涯作为一个研究科学家在学术界。19，姓名和学位（S）Yoland Smith，博士20. 21.第二十一章.研究兴趣/领域研究代谢型谷氨酸受体在基底神经节附近的生理作用22。本项目的主要目的是了解代谢感受性谷氨酸受体（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，基底神经节是一组控制运动行为的亚皮层核团，也具有认知功能。 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的激活在许多脑区产生重要和持久的作用，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mGluR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标。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在活体大鼠脑切片中使用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是脱敏的，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。PHS 416-1（1998年12月修订版）表格第2页BB CC IndivTidaubale NoRfSAConAtpepnlitcsation NAME（Las_ P#6/sit，smik/d，d/e/ni#al）Olga页码（编号页在申请表底部。不得使用第1节--申请人sufr_essuchas. Ca 5，B.）首页（第1-8、15项）、表格页2（第16-I、8、22项）和目录==

18. GOALS FOR FELLOWSHIP TRAINING AND CAREER My goals under this fellowship are to examine the functions of metabotropic glutamate receptors in the rat Ilobus pallidus and to establish how these receptors modulate the activity of this brain region. The output of globus pallidus is undermined in many disorders of the central nervous system and the ultimate goal of this fellowship is to determine whether metabotropic glutamate receptors can be successfully used as therapeutic targets in treatment or management of these diseased states. Under this fellowship I intend to improve and broaden my technical skills in eleetrophysiology and immunocytochemistry. With the guidance of my sponsor I hope to progress in my ability to plan experiments, critically analyze and interpret data, and to disclose the significance of my results. At the same time, I will attend scientific meetings and seminars where I plan to present and discuss my findings, which will facilitate my ability to communicate with fellow scientists. Development of these skills will be essential in my future career as a research scientist in academia. 19, NAME AND DEGREE(S) Yoland Smith, Ph.D. 20. PosmoN/RANK Associate Professor 21. RESEARCH INTERESTS/AREAS To study the physiological roles of metabotropic glutamate receptors in the vicinity of basal ganglia 22. DESCRIPTION (Do not exceed space provided) The primary objective of this project is tounderstand how metabolxopic glutamate receptors (mGluRs) shape the output of the globus paliidus (GP), an intrinsic component of the basal ganglia, a group of subeortical nuclei that control motor behavior and also have cognitive ftmetions. 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 ofmGluRs 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 therapentie 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 synaptie transmission in the GP, and 3) on the desensitization mechanisms of some postsynaptie mGluRs in the GP. The functional roles ofmGluRs and their desensitization mechanisms will be studied using in vitro eleetrophysiologieal recordings in living rat brain slices. Commercially available agonists and antagonists to all groups ofmGluRs will be utilized. We intend to study the desensitization mechanisms ofmGluRs 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. PHS 416-1 (Rev. 12/98) Form Page 2 BB CC IndivTidaubale NoRfSAConAtpepnlitcsation NAME (Las_ P#6/sit,smik/d,d/e/ni#al)Olga Page Numbers (Numberpagesconsecugve/y atthebottomthroughouthe application. Do not use Section 1--Applicant sufr_essuchas.Ca5, b.) Face Page (Items 1-8, 15), Form Page 2 (Items 16-I 8, 22), and Table of Content ========================================Section End===========================================