This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.In this project we used a combination of high resolution immunoelectron microscopy, patch clamp recording technique and gene deletion method to characterize various aspects of the localization, function and trafficking mechanisms of metabotropic glutamate receptors (mGluRs) in the basal ganglia. Three main studies related to this project have been achieved during the past year. The key findings of these studies can be summarized as follows: (1) In collaboration with Dr Paul Worley at Johns Hopkins University, we have demonstrated that the deletion of Homer genes have significant effects on the expression and the pre-synaptic localization of group I metabotropic glutamate receptors in normal mice and MPTP-treated mice model of Parkinson's disease. (2) Using the in vitro patch clamp recording technique in rat brain slices, we demonstrated that the functional and pharmacological properties of group I mGluRs in the globus pallidus are highly dependent on dopaminergic transmission, suggesting significant functional changes of these receptors in Parkinson's disease. (3) In collaboration with Pisani and colleagues in Italy, we demonstrated a significant degree of co-localization of the two group I mGluRs (mGluR1a and mGluR5) in individual parvalbumin-containing interneurons in the rat striatum. Surprisingly, despite such a high degree of co-existence, in vitro patch clamp recordings showed that activation of mGluR1 only have significant physiological effects on the membrane polarization of these interneurons. These data highlight the complexity and multifarious roles of these receptors in basal ganglia. Together, our findings provide important information on the localization, function and plasticity of group I mGluRs in basal ganglia, a novel highly promising target for Parkinson's disease pharmacotherapy.
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