Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells.

Metabotropic glutamate receptors (mGluRs) are a family of proteins that have seven transmembrane segments and that couple to G proteins. They differ from ionotropic glutamate receptors in that they do not form ion channels but instead affect intracellular chemical messenger systems. Eight genes coding for different subtypes of mGluRs have been identified to date and numbered accordingly in the order in which the cDNAs were cloned. Based on their principal signal-transduction capabilities in recombinant expression systems and sequence similarities, the family of mGluR subtypes is subdivided into three groups. Group 1 mGluRs (consisting of mGluR1 and 5) functionally couple to phospholipase C and affect the IP3/Ca2+ signaling pathway. The subtypes of group 2 (mGluR2 and 3) and group 3 (mGluR4, 6 7 and 8) inhibit adenylate cyclase and, thereby, mediate a decrease in cAMP concentration. All mGluR subtypes are found in the cerebellar cortex with the exception of mGluR6 which is exclusively expressed in the retina. At the parallel fiber-Purkinje cell synapses mGluR1 is localized in the peri- and extra-synaptic membrane of Purkinje cells. The main focus of this review deals with the functions of this postsynaptically localized mGluR1. These functions include (i) mediation of an inward current and a slow excitatory postsynaptic potential, and (ii) a role in induction of parallel fiber-Purkinje cell long-term depression. We discuss the mechanism underlying the mGluR1-mediated postsynaptic current as well as current theories on the role of mGluR1 in parallel fiber-Purkinje cell long-term depression.