| The complexity and diversity of glutamatergic signals arise, in part, due to the existence of many types of glutamate receptors. Metabotropic glutamate receptors (mGluRs), which comprise one family of glutamate receptors, collectively exemplify an astounding variety in effects of L-glutamate in the CNS. Eight mGluRs have been cloned and they have been sub-divided into three groups based on their sequence homology, coupling to specific second messenger signaling cascades, and pharmacology.; The overall focus of this dissertation is to examine the contribution of mGluRs in modulating activity of one CNS nucleus, the globus pallidus (GP), an integral component of a group of sub-cortical nuclei, termed basal ganglia. Disclosing physiological roles of mGluRs in the GP will not only shed light on the contribution of these receptors to modulating neuronal activity in this nucleus, but it will also aid in the assessment of mGluRs as targets for pharmacotherapy in treatment of basal ganglia-related neurological disorders.; Using the whole-cell patch-clamp recording technique in rat GP slices, we examined the involvement of mGluR sub-types in modulating neuronal excitability and excitatory synaptic transmission. We found that activation of mGluR1 depolarizes GP neurons via modulation of plasma membrane channels, while activation of mGluR5 leads to the desensitization of mGluR1 in a protein kinase C-dependent manner. Functional coupling of the group I mGluR sub-types in the GP is dependent on activity of dopamine receptors, because blockade of dopamine receptors or dopaminergic depletion alters the signaling properties of mGluR1 and 5.; While activation of group I mGluRs affects neuronal excitability via modulation of plasma membrane channels, activation of group II or III mGluRs affects excitatory neurotransmission via regulation of glutamate release in the GP. Activation of group II mGluR2 or group III mGluR7 inhibits glutamate release in the GP.; Our data reveal that some of the signaling properties of mGluRs in the GP are unique to this nucleus further providing evidence that these receptors function to diversify glutamatergic signals in the CNS. In addition, disclosed physiological roles of mGluRs in the GP corroborate their therapeutic potential in the treatment of basal ganglia-related disorders such as Parkinson's disease. |
