TY - JOUR T1 - Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms JF - Pharmacological Reviews JO - Pharmacol Rev DO - 10.1124/pr.109.001735 SP - pr.109.001735 AU - Clare M. Gladding AU - Stephen M. Fitzjohn AU - Elek Molnár Y1 - 2009/11/19 UR - http://pharmrev.aspetjournals.org/content/early/2009/11/19/pr.109.001735.abstract N2 - The ability to modify synaptic transmission between neurons is a fundamental process of the nervous system that is involved in development, learning, and disease. Thus, synaptic plasticity is the ability to bidirectionally modify transmission, where long-term potentiation and long-term depression (LTD) represent the best characterized forms of plasticity. In the hippocampus, two main forms of LTD coexist that are mediated by activation of either N-methyl-d-aspartic acid receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). Compared with NMDAR-LTD, mGluR-LTD is less well understood, but recent advances have started to delineate the underlying mechanisms. mGluR-LTD at CA3:CA1 synapses in the hippocampus can be induced either by synaptic stimulation or by bath application of the group I selective agonist (R,S)-3,5-dihydroxyphenylglycine. Multiple signaling mechanisms have been implicated in mGluR-LTD, illustrating the complexity of this form of plasticity. This review provides an overview of recent studies investigating the molecular mechanisms underlying hippocampal mGluR-LTD. It highlights the role of key molecular components and signaling pathways that are involved in the induction and expression of mGluR-LTD and considers how the different signaling pathways may work together to elicit a persistent reduction in synaptic transmission.© 2009 by The American Society for Pharmacology and Experimental Therapeutics ER -