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Immunohistochemical localization of subtype 4a metabotropic glutamate receptors in the rat and mouse basal ganglia
Author(s) -
Bradley Stefania Risso,
Standaert David G.,
Rhodes Kenneth J.,
Rees Howard D.,
Testa Claudia M.,
Levey Allan I.,
Conn P. Jeffrey
Publication year - 1999
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19990428)407:1<33::aid-cne3>3.0.co;2-g
Subject(s) - globus pallidus , basal ganglia , biology , substantia nigra , striatum , neuroscience , metabotropic glutamate receptor , cerebellum , metabotropic receptor , glutamate receptor , receptor , central nervous system , biochemistry , dopamine , dopaminergic
Recent studies suggest that metabotropic glutamate receptors (mGluRs) may play a significant role in regulating basal ganglia functions. In this study, we investigated the localization of mGluR4a protein in the mouse and rat basal ganglia. Polyclonal antibodies that specifically react with the metabotropic glutamate receptor subtype mGluR4a were produced and characterized by Western blot analysis. These antibodies recognized a native protein in wild‐type mouse brain with a molecular weight similar to the molecular weight of the band from a mGluR4a‐transfected cell line. The immunoreactivity was absent in brains of knockout mice deficient in mGluR4. mGluR4a immunoreactivity was most intense in the molecular layer of the cerebellum. We also found a striking mGluR4a immunoreactivity in globus pallidus, and moderate staining in substantia nigra pars reticulata and entopeduncular nucleus. Moderate to low mGluR4a immunoreactivity was present in striatum and other brain regions, including hippocampus, neocortex, and thalamus. Double labeling with mGluR4a antibodies and antibodies to either a dendritic marker or a marker of presynaptic terminals suggest a localization of mGluR4a on presynaptic terminals. Immunocytochemistry at electron microscopy level confirmed these results, revealing that in the globus pallidus, mGluR4a is mainly localized in presynaptic sites in axonal elements. Finally, quinolinic acid lesion of striatal projection neurons decreased mGluR4a immunoreactivity in globus pallidus, suggesting a localization of mGluR4a on striatopallidal terminals. These data support the hypothesis that mGluR4a serves as a presynaptic heteroreceptor in the globus pallidus, where it may play an important role in regulating g‐amino‐n‐butyric acid (GABA) release from striatopallidal terminals. J. Comp. Neurol. 407:33–46, 1999. © 1999 Wiley‐Liss, Inc.