title: Glycine induces bidirectional modifications in N-methyl-D-aspartate receptor-mediated synaptic responses in hippocampal CA1 neurons.
abstract: Glycine can persistently potentiate or depress AMPA responses through differential actions on two binding sites: NMDA and glycine receptors. Whether glycine can induce long-lasting modifications in NMDA responses, however, remains unknown. Here, we report that glycine induces long-term potentiation (LTP) or long-term depression (LTD) of NMDA responses (Gly-LTP(NMDA) or Gly-LTD(NMDA)) in a dose-dependent manner in hippocampal CA1 neurons. These modifications of NMDA responses depend on NMDAR activation. In addition, the induction of Gly-LTP(NMDA) requires binding of glycine with NMDARs, whereas Gly-LTD(NMDA) requires that glycine bind with both sites on NMDARs and GlyRs. Moreover, activity-dependent exocytosis and endocytosis of postsynaptic NMDARs underlie glycine-induced bidirectional modification of NMDA excitatory postsynaptic currents. Thus, we conclude that glycine at different levels induces bidirectional plasticity of NMDA responses through differentially regulating NMDA receptor trafficking. Our present findings reveal important functions of the two glycine binding sites in gating the direction of synaptic plasticity in NMDA responses.
authors.affiliation: From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029.
authors.forename: Fang
authors.initials: F
authors.lastname: Ji
authors.affiliation: From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China, and.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Chen
authors.affiliation: From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China lu@njmu.edu.cn luwei@seu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005998:Glycine / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: C096392:Grin3a protein, rat; D008562:Membrane Glycoproteins; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D005998:Glycine
keywords: Glycine; Glycine Receptor; Ionotropic Glutamate Receptor; LTD; LTP; Membrane Trafficking; Membrane Transport; NMDA Receptors; Synaptic Plasticity