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.
