Induction of long-lasting depression by (+)-alpha-methyl-4-carboxyphenylglycine and other group II mGlu receptor ligands in the dentate gyrus of the hippocampus in vitro

Application of several well characterized group II mGlu receptor ligands wa s found to induce a long-lasting depression of synaptic transmission in the medial perforant path of the dentate gyrus. These ligands were N-acetylasp artylglutamate (NAAG), which is a dipeptide located in the brain and possib ly functioning as a neurotransmitter, two agents widely used previously as mGluR antagonists, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), and (S)- alpha-ethylglutamate (EGLU), and the well characterized group II mGluR agon ist (2S,1R,2R,3R)-2-(2S,1'R,2'R,3'R)-2(2'3'-dicarboxycyclopropyl)glycine (D CG-IV). It is postulated that all these ligands induced the long-lasting de pression by an agonist/partial agonist action at group II mGlu receptor. Th e long-lasting depression induced by the ligands showed mutual occlusion wi th low frequency stimulation-induced long-term depression, demonstrating co mmon induction or maintenance mechanisms. The induction of the long-lasting depression by the mGlu receptor ligands are suggested to occur postsynapti cally as the induction was not associated with a change in paired pulse dep ression of excitatory postsynaptic potentials (EPSPs). (C) 1999 Elsevier Sc ience B.V. All rights reserved.