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 was found to induce a long-lasting depression of synaptic transmission in the medial perforant path of the dentate gyrus. These ligands were N-acetylaspartylglutamate (NAAG), which is a dipeptide located in the brain and possibly 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 agonist (2S,1R,2R,3R)-2-(2S,1'R,2'R,3'R)-2(2'3'-dicarboxycyclopropyl)glyci ne (DCG-IV). It is postulated that all these ligands induced the long-lasting depression by an agonist/partial agonist action at group II mGlu receptor. The long-lasting depression induced by the ligands showed mutual occlusion with low frequency stimulation-induced long-term depression, demonstrating common induction or maintenance mechanisms. The induction of the long-lasting depression by the mGlu receptor ligands are suggested to occur postsynaptically as the induction was not associated with a change in paired pulse depression of excitatory postsynaptic potentials (EPSPs).