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