Metabotropic Receptors in Globus Pallidus

18. 我的研究目标是研究大鼠苍白叶中代谢性谷氨酸受体的功能，并确定这些受体如何调节这一大脑区域的活动。在中枢神经系统的许多疾病中，苍白球的输出被破坏，本研究的最终目的是确定代谢性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。在这项研究中，我打算提高和扩大我在电生理学和免疫细胞化学方面的技术技能。在我的赞助人的指导下，我希望提高我的实验计划能力，批判性地分析和解释数据的能力，并揭示我的结果的意义。同时，我将参加科学会议和研讨会，在那里我计划展示和讨论我的发现，这将有助于我与其他科学家交流的能力。这些技能的发展对我未来作为学术界研究科学家的职业生涯至关重要。姓名与学位约兰德·史密斯博士波兹蒙/RANK副教授研究代谢性谷氨酸受体在基底神经节附近的生理作用。本项目的主要目标是了解代谢异位谷氨酸受体（mGluRs）如何影响白球（GP）的输出，GP是基底节区的固有组成部分，基底节区是一组控制运动行为并具有认知功能的亚皮质核。GP的活动在基底神经节的一些疾病中被破坏，如帕金森氏病、亨廷顿舞蹈病和抑郁症。mglurs的激活在许多大脑区域产生重要和持久的影响，这使它们成为治疗神经系统疾病的有吸引力的药理靶点。本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，以及3)GP中一些突触后mGluRs的脱敏机制。我们将利用活体大鼠脑片体外电生理记录研究mglurs的功能作用及其脱敏机制。将使用市售的所有mglur组的激动剂和拮抗剂。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作用。总之，这项工作将揭示mGluRs在GP中的功能及其在治疗基底神经节疾病方面的有用潜力。PHS 416-1 （Rev. 12/98）表格第2页BB CC个人填写norfsaconatpeplitcsation NAME (last_p# 6/sit,smik/d,d/e/ni#al)Olga页码（numberpages连续/在整个应用程序的底部）。不要使用第1节——申请人sufr_essuchas。Ca5, b)。脸(项目1 - 8、15页),表单页面2(项目我8日22),和表的内容 ======================================== 节结束 ===========================================

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===========================================