Localization and expression of group I metabotropic glutamate receptors in the mouse striatum, globus pallidus, and subthalamic nucleus: regulatory effects of MPTP treatment and constitutive Homer deletion.

Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, regulate activity in the globus pallidus (GP) and subthalamic nucleus (STN). To test whether the localization of group I mGluRs is altered in parkinsonism, we used immunoelectron microscopy to analyze the subcellular and subsynaptic distribution of mGluR1a and mGluR5 in GP and STN of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Homer1 and Homer2 knock-out mice were used to assess the role of Homer in MPTP-induced redistribution of group I mGluRs. We also examined the effects of MPTP on the expression levels of group I mGluRs and Homer proteins in GP and striatum. MPTP treatment significantly reduced the expression levels of H1a and mGluR1a in striatum but not in GP. Although light microscopy did not reveal noticeable effects of MPTP treatment on the distribution of group I mGluRs and Homer proteins in GP and STN, specific changes in the ultrastructural localization of mGluR1a were found in MPTP-treated normal and Homer knock-out mice. An increase in the expression of presynaptic axonal and terminal mGluR1a labeling and an increased level of mGluR1a immunoreactivity in the postsynaptic specialization of putative GABAergic synapses were among the most significant effects induced by dopamine depletion. However, neither of these changes was found for mGluR5, which, in contrast, displayed complex regulatory alterations in its subsynaptic distribution in response to Homer deletion and MPTP lesion. Thus, nigrostriatal dopaminergic lesion and Homer deletion lead to changes in the trafficking of group I mGluRs in vivo that are specific to receptor subtypes and brain areas.