METABOTROPIC GLUTAMATE-RECEPTOR MESSENGER-RNA EXPRESSION IN THE BASALGANGLIA SF THE RAT

Metabotropic glutamate receptors (mGluRs) couple the actions of glutam ate to intracellular second messenger systems through G-proteins. The mGluRs play an important role in the regulation of basal ganglia funct ion. Ligand binding studies have revealed that the basal ganglia conta in at least two pharmacological types of metabotropic binding sites. A gonists of mGluRs can affect both in vitro electrophysiologic response s of striatal neurons and motor behavior in vivo. Recently, cDNAs enco ding five mGluRs have been cloned, each with distinct structural and p harmacological properties. In order to elucidate the function of these receptors in the biology of the extrapyramidal motor system, we have used in situ hybridization to examine the regional and cellular expres sion patterns of mGluR1-mGluR5 in the adult rat basal ganglia. In the striatum, all of these mGluRs were present in widely varying relative densities and cellular patterns. MGluR5 was particularly prominent, an d exhibited a heterogeneous cellular distribution, with labeled and un labeled populations of neurons. MGluR2 was expressed in a small popula tion of large polygonal striatal neurons. The subthalamic nucleus was the only other basal ganglia structure that expressed mGluR2. Distinct cellular distributions of mGluR expression were also observed within the nucleus accumbens, globus pallidus, ventral pallidum, and substant ia nigra pars reticulata. MGluR3 was expressed in glia in all basal ga nglia structures, but was observed in neurons only in the striatum, su bstantia nigra pars reticulata, and very weakly in the subthalamic nuc leus. Comparison of the restricted mGluR2 and mGluR3 mRNA distribution s with that of metabotropic ligand binding sites supports a possible p resynaptic location for these receptors in the basal ganglia. MGlUR1 w as the only mGluR message prominently expressed in the dopaminergic ne urons of the substantia nigra pars compacta, suggesting the involvemen t of this receptor in the regulation of dopamine release from nigrostr iatal terminals.