Schematic representation of mGluRs at the synapse. In general, group I mGluRs (green) are localized postsynaptically, and group II (blue) and III (red) receptors are localized in presynaptic locations, although exceptions occur. In presynaptic locations, mGluRs 2, 3, 4, and 8 are generally found in extrasynaptic locations, and mGluR7 is highly localized to the active zone (). Group II and III receptors inhibit release of glutamate (left, yellow circles) or GABA (right, red circles), whereas group I receptors promote release when present. At the postsynaptic terminal, the glutamate gated ion channels N-methyl-D-asparate (NMDA), α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and kainate respond to glutamate with increases in intracellular sodium or calcium, promoting cell excitability. Group I mGluRs signal via Gq proteins to increase intracellular calcium; additionally, mGluR5 and NMDA receptors are closely linked signaling partners reciprocally regulated by phosphorylation (black circle) (). Postsynaptic mGluR2/3 and GABAB1/2 receptors couple to cAMP inhibition. GABAA chloride channels (pink) modulate intracellular chloride. Expression of mGluR3 and mGluR5 on glia is now emerging as another key site for mGluR regulation of synaptic activity, although the signaling pathways and consequences of receptor activation on these cells are not presently well understood.