DIFFERENTIAL EXPRESSION OF METABOTROPIC GLUTAMATE RECEPTORS IN THE HIPPOCAMPUS AND ENTORHINAL CORTEX OF THE RAT

Metabotropic glutamate receptors (mGluRs) have been implicated in a nu mber of hippocampal functions including learning and memory. Five subt ypes have been molecularly and pharmacologically characterized. Using in situ hybridization with oligonucleotide probes selective for these five mGluRs, we have found that each has a unique pattern of expressio n in the hippocampus and entorhinal cortex. mGluR1 is expressed predom inantly in the dentate gyrus and CA3. mGluR2 is enriched in the dentat e gyrus and inner layer of the entorhinal cortex. mGluR3 is also expre ssed in these two structures, but unlike all the other mGluRs, is foun d in white matter areas as well. mGluR4 is present predominantly in CA 2 while mGluR5 is concentrated in most regions of the hippocampus and entorhinal cortex. Comparative analysis of the distributions of these receptors with that of the components of their putative downstream sig nal transduction mechanisms suggests that mGluR5 may be the main subty pe of mGluR which mediates the excitatory actions of glutamate in CA1 and could contribute to the elevation of calcium levels found in CA1 p yramidal neurons in long term potentiation and in ischemic/hypoxic inj ury. mGluR2 and mGluR3, the main subtypes contributing to the inhibito ry actions of glutamate, are absent in CA1. Thus, the mGluR-mediated e xcitatory actions of glutamate can occur in all regions of the hippoca mpus whereas the mGluR-mediated inhibitory actions of glutamate may be restricted to the dentate gyrus and CA3.