IMMUNOCYTOCHEMICAL LOCALIZATION OF GROUP-III METABOTROPIC GLUTAMATE RECEPTORS IN THE HIPPOCAMPUS WITH SUBTYPE-SPECIFIC ANTIBODIES

The metabotropic glutamate receptors (mGluRs) mGluR4 and mGluR7 have b een postulated to serve as presynaptic autoreceptors in the hippocampa l formation. The cellular and synaptic localization of these proteins in the hippocampus, however, is not known. Polyclonal antibodies that specifically react with mGluR4a or mGluR7 were produced and used for i mmunocytochemical localization of these receptor proteins, Immunoblot analysis with mGluRs expressed in stably transfected baby hamster kidn ey cells suggests that each of the antibodies reacts specifically with the appropriate mGluR subtype but not with other mGluRs, Both antibod ies recognized native proteins in rat brain with molecular weights sim ilar to the molecular weights of the bands in mGluR-transfected cell l ines. The distribution of mGluR4a immunoreactivity was fairly uniform in all brain regions. Immunoreactivity for mGluR7 was variable in diff erent brain regions and closely paralleled the previously reported dis tribution of mGluR7 mRNA. Immunocytochemistry with light and electron microscopy (EM) revealed that immunoreactivities for mGluR4a and mGluR 7 are widely but differentially distributed throughout the hippocampal formation, Staining with antibodies directed against mGluR4a was inte nse in cell bodies and dendrites of pyramidal cells, granule cells, an d scattered interneurons. Analysis at the EM level revealed postsynapt ic mGluR4a localization al asymmetrical (presumably glutamatergic) syn apses and presynaptic localization at both asymmetrical and symmetrica l synapses. Immunoreactivity for mGluR7 revealed largely presynaptic l ocalization of this receptor at asymmetrical but not symmetrical synap ses. These data are consistent with a largely presynaptic role of mGlu R7 in the hippocampus and suggest that mGluR4 may have both presynapti c and postsynaptic functions.