title: NR3A-containing NMDARs promote neurotransmitter release and spike timing-dependent plasticity.
abstract: Recent evidence suggests that presynaptic-acting NMDA receptors (preNMDARs) are important for neocortical synaptic transmission and plasticity. We found that unique properties of the NR3A subunit enable preNMDARs to enhance spontaneous and evoked glutamate release and that NR3A is required for spike timing-dependent long-term depression in the juvenile mouse visual cortex. In the mature cortex, NR2B-containing preNMDARs enhanced neurotransmission in the absence of magnesium, indicating that presynaptic NMDARs may function under depolarizing conditions throughout life. Our findings indicate that NR3A relieves preNMDARs from the dual-activation requirement of ligand-binding and depolarization; the developmental removal of NR3A limits preNMDAR functionality by restoring this associative property.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Rylan S
authors.initials: RS
authors.lastname: Larsen
authors.forename: Rebekah J
authors.initials: RJ
authors.lastname: Corlew
authors.forename: Maile A
authors.initials: MA
authors.lastname: Henson
authors.forename: Adam C
authors.initials: AC
authors.lastname: Roberts
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Isabel
authors.initials: I
authors.lastname: Pérez-Otaño
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Weinberg
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Philpot
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
chemical_list: C464437:NR3A NMDA receptor; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008274:Magnesium