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lüll Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms Gladding CM; Fitzjohn SM; Molnar EPharmacol Rev 2009[Dec]; 61 (4): 395-412The 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.|Animals[MESH]|Excitatory Amino Acid Agonists/pharmacology[MESH]|Humans[MESH]|Long-Term Synaptic Depression/drug effects/*physiology[MESH]|Neurons/drug effects/metabolism[MESH]|Receptors, Metabotropic Glutamate/genetics/metabolism/*physiology[MESH] |