Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites

The metabotropic glutamate receptors (mGluRs) have distinct distribution pa tterns in the CNS but subtypes within group I or group III mGluRs share sim ilar ultrastructural localization relative to neurotransmitter release site s: group I mGluRs are concentrated in an annulus surrounding the edge of th e postsynaptic density, whereas group III mGluRs are concentrated in the pr esynaptic active zone. One of the group II subtypes, mGluR2. is expressed i n both pre- and postsynaptic elements, having no close association with syn apses. In order to determine if such a distribution is common to another gr oup II subtype. mGluR3, an antibody was raised against a carboxy-terminus o f mGluR3 and used for light and electron microscopic immunohistochemistry i n the mouse CNS. The antibody reacted strongly with mGluR3, but it also rea cted, though only weakly, with mGluR2. Therefore, to examine mGluR3-selecti ve distribution, we used mGluR2-deficient mice as well as wild-type mice. S trong immunoreactivity for mGluR3 was found in the cerebral cortex. striatu m. dentate gyrus of the hippocampus, olfactory tubercle, lateral septal nuc leus, lateral and basolateral amygdaloid nuclei. and nucleus of the lateral olfactory tract. Pre-embedding immunoperoxidase and immunogold methods rev ealed mGluR3 labeling in both presynaptic an postsynaptic elements, and als o in glial profiles. Double labeling revealed that the vast majority of mGl uR3 in presynaptic elements is not closely associated with glutamate and GA BA release sites in the striatum and thalamus, respectively. However. in th e spines of the dentate granule cells, the highest receptor density was fou nd in perisynaptic sites (20% of immunogold particles within 60 nm from the edge of postsynaptic membrane specialization) followed by a decreasing rec eptor density away from the synapses (to similar to 5% of particles per 60 nm). Furthermore, 19% of immunogold particles were located in asymmetrical postsynaptic specialization, indicating an association of mGluR3 to glutama tergic synapses. The present results indicate that the localization of mGlu R3 is rather similar to that of group I mGluRs in the postsynaptic elements , suggesting a unique functional role of mGluR3 in glutamatergic neurotrans mission in the CNS. (C) 2001 IBRO. Published by Elsevier Science Ltd. All r ights reserved.