Research Projects

The central nervous system (CNS) is a major excitatory neurotransmitter that activates ionotropic glutamate receptors (NMDARs, AMPARs, and kainate receptors) and metabotropic glutamate receptors (mGluRs). Group I mGluRs, consisting of mGluR1 and mGluR5, play crucial roles in synaptic plasticity, learning, and memory. mGluR-mediated AMPA receptor endocytosis is believed to be the cellular correlate for mGluR-dependent synaptic plasticity. Group I mGluRs have been implicated in various neuropsychiatric disorders like Fragile X syndrome and autism. The appropriate delivery of group I mGluRs to the cell surface is crucial for proper signaling. They undergo desensitization and internalization upon ligand binding, which could regulate various activities of these receptors. Regulation of mGluR trafficking provides a powerful means to modulate many synaptic functions. Dopamine plays an important role in hippocampus-dependent learning and memory. Specific lesion of these projections to the hippocampus impairs spatial learning in rats. An association has been found between memory formation and the coactivation of midbrain dopamine areas and the hippocampus, indicating a potential crosstalk between the dopaminergic system and the glutamatergic system in the hippocampus. A better understanding of the mechanisms underlying dopamine-mediated mGluR trafficking and mGluR-mediated AMPAR endocytosis is critical for understanding its physiological and therapeutic implications. This proposal aims to investigate the role of dopamine in the trafficking of group I mGluRs and how it affects mGluR-mediated AMPAR endocytosis in hippocampal neurons using molecular biological, cell biological, biochemical, and imaging techniques.