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

• Type of Material: Article
• Authors: Masaaki Kuwajima, Emory University; Marlin H. Dehoff, Johns Hopkins University; Teiichi Furuichi, RIKEN Brain Science Institute; Paul F. Worley, Johns Hopkins University; Randy Hall, Emory University; Yoland Smith, Emory University
• Language: English
• Date: 2007-06-06
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2007 Society for Neuroscience.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.3819-06.2007
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 27
• Issue: 23
• Start Page: 6249
• End Page: 6260
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health (NIH) to Y.S., R.A.H., and P.F.W.; the Yerkes Center NIH base grant (RR00165); and the W. M. Keck Foundation (a Distinguished Young Scholar in Medical Research award to R.A.H.).
• Keywords: TRANSMISSION; Science & Technology; FOREBRAIN; plasticity; MPTP; PROTEINS; PARKINSONS-DISEASE; Neurosciences & Neurology; IMMUNOHISTOCHEMICAL LOCALIZATION; BASAL-GANGLIA; SUBSTANTIA-NIGRA; RAT; Neurosciences; ultrastructure; immunogold; basal ganglia; ASSOCIATION; ACTIVATION; Parkinson's disease; Life Sciences & Biomedicine
• Research Categories: Biology, Neuroscience

Abstract

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.