IMMUNOHISTOCHEMICAL LOCALIZATION OF METABOTROPIC GLUTAMATE RECEPTORS MGLUR1A AND MGLUR2 3 IN THE RAT BASAL GANGLIA/

Metabotropic glutamate receptors (mGluRs), which couple glutamate to s econd messengers, have important roles in the regulation of movement b y the basal ganglia. We used two polyclonal antisera to mGluR1a and mG luR2/3 and confocal laser microscopy to investigate the localization o f these receptors in the basal ganglia of the rat. The mGluRs were vis ualized in combination with an antibody to tyrosine hydroxylase (TH), an antibody to microtubule-associated protein 2 (MAPS, a dendritic mar ker), or SV2 (an antibody to a protein associated with presynaptic ter minals). In the neostriatum, punctate mGluR1a immunoreactivity (ir) wa s present in the neuropil. This staining did not colocalize with MAP2- ir or SV2-ir and was not altered by decortication or unilateral B-hydr oxydopamine (6-OHDA) lesions. In the globus pallidus and substantia ni gra pars reticulata, however, mGluR1a-ir was tightly clustered along l arge MAP2-ir dendrites. In contrast to the variations in mGluR1a-ir st aining, similar punctate neuropil mGluR2/3-ir staining was observed wi thin all basal ganglia structures. In the neostriatum, these puncta we re abundant; unlike mGluR1a, many mGluR2/3-ir puncta colocalized with SV2-ir, and striatal mGluR2/3-ir puncta were markedly reduced in numbe r after decortication. Neither mGluR1a-ir nor mGluR2/3-ir could be det ected in TH-ir soma within substantia nigra pars compacta, or in TH-ir striatal terminals. Overall, our observations suggest that mGluR1a an d mGluR2/3 receptors have distinct cellular localizations in different components of the basal ganglia circuitry and are likely to subserve distinct functions. Our data support the presence of mGluR2/3 on the t erminals of corticostriatal afferents, where they may regulate glutama te release. In contrast, mGluR1a appears to be a postsynaptic receptor of neurons in the neostriatum, globus pallidus, and substantia nigra pars reticulata. (C) 1998 Wiley-Liss, Inc.