Immunohistochemical localization of the mGluR1β metabotropic glutamate receptor in the adult rodent forebrain: Evidence for a differential distribution of mGluR1 splice variants

Alternative splicing has been shown to occur at the metabotropic glutamate receptor 1 (mGluR1) gene. Three main isoforms that differ in their carboxy-termini have been described so far and named mGluR1α, mGluR1β and mGluR1c. These variants when expressed in recombinant systems all activate phospholipase C, although the [Ca²⁺] signals generated have different kinetics. Tissue distribution studies of specific mGluR1 splice variants are limited to the mGluR1α isoform. In the present work, we examined the localization of mGluR1β in the adult rat and mouse forebrain by using a specific antipeptide antibody. Furthermore, the mGluR1β immunostaining was compared with that obtained with antibodies specific for mGluR1α or with a pan-mGluR1 antibody which recognizes all isoforms. mGluR1β-like immunoreactivity (LI) was found confined to the neuropil and neuronal perikarya and appeared discretely distributed in the rodent forebrain. Differential cellular distribution between mGluR1α and mGluR1β was observed. In the hippocampus, mGluR1α-LI was restricted to non-principal neurons in all fields, whereas mGluR1β-LI was strongest in principal cells of the CA3 field and dentate granule cells but absent in CA1. We have also shown that the vast majority of neurons in the striatum express mGluR1. The predominant form appeared to be mGluR1β, with a distribution pattern reflecting the patch-matrix organization of the striatum. The specificity of the immunoreactivity described for mGluR1 splice variants was confirmed in mGluR1-deficient mice. The observation of a different cellular and regional distribution of mGlUR1 splice variants, in particular in the hippocampus, suggests that they may mediate different roles in synaptic transmission.