title: Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity.
abstract: Hebbian, or associative, forms of synaptic plasticity are considered the molecular basis of learning and memory. However, associative synaptic modifications, including long-term potentiation (LTP) and depression (LTD), can form positive feedback loops which must be constrained for neural networks to remain stable. One proposed constraint mechanism is metaplasticity, a process whereby synaptic changes shift the threshold for subsequent plasticity. Metaplasticity has been functionally observed but the molecular basis is not well understood. Here, we report that stimulation which induces LTP recruits GluN2B-lacking GluN1/GluN3 NMDA receptors (NMDARs) to excitatory synapses of hippocampal pyramidal neurons. These unconventional receptors may compete against conventional GluN1/GluN2 NMDARs to favor synaptic depotentiation in response to subsequent "LTP-inducing" stimulation. These results implicate glycinergic GluN1/GluN3 NMDAR as molecular brakes on excessive synaptic strengthening, suggesting a role for these receptors in the brain that has previously been elusive.
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Rozeboom
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Bridget N
authors.initials: BN
authors.lastname: Queenan
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Partridge
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Farnham
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
authors.forename: Jian-Young
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicini
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA. Electronic address: Daniel.Pak@georgetown.edu.
authors.forename: Daniel T S
authors.initials: DT
authors.lastname: Pak
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: C584082:GluN3A protein, mouse; C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate
keywords: GluN3; Glycinergic; LID; LTP; Metaplasticity; NMDA receptor