ArticleMolecular pharmacology2016
GluN2D-Containing N-methyl-d-Aspartate Receptors Mediate Synaptic Transmission in Hippocampal Interneurons and Regulate Interneuron Activity.
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Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76citing papers in PubMed
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76 citing papers in PubMed, 110 citations in OpenAlex.
- GluN2D NMDA Receptors: Bridging Physiology and Pathology.Biological psychiatry · 2026Review
- Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine.Cell reports · 2026Article
- Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency.Science advances · 2026Article
- A depression-like phenotype is associated with discrete defects in the primary hippocampal circuit.Translational psychiatry · 2026Article
- Inhibition of GluN2B-containing N-methyl-D-aspartate receptors by radiprodil.Brain : a journal of neurology · 2026Article
- Esketamine/Ketamine: Dual-Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Heterosynaptic NMDA receptor plasticity in hippocampal dentate granule cells.Frontiers in synaptic neuroscience · 2026Article
- The NMDA receptor subunit GluN2D is a potential target for rapid antidepressant action.Nature communications · 2025Article
- Synaptic dysregulation in a mouse model of GRIN2D developmental and epileptic encephalopathy.Brain : a journal of neurology · 2025Article
- Enhancement of hippocampal interneuron excitability by NMDA receptor positive allosteric modulation.The Journal of physiology · 2025Article
- Selective enhancement of the interneuron network and gamma-band power via GluN2C/GluN2D NMDA receptor potentiation.The Journal of physiology · 2025Article
- Activation of GluN2D-containing NMDA receptors promotes development of axons and axon-carrying dendrites of cortical interneurons.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- The Effects of miR-22-3p on Differentiation of Human Dental Pulp Stem Cells into Neural Progenitor-Like Cells.Molecular neurobiology · 2025Article
- Computational modeling of ketamine-induced changes in gamma-band oscillations: The contribution of parvalbumin and somatostatin interneurons.PLoS computational biology · 2025Article
- Structural basis for channel gating and blockade in tri-heteromeric GluN1-2B-2D NMDA receptor.Neuron · 2025Article
- GluN2D-containing NMDA receptors in parvalbumin neurons in the nucleus accumbens regulate nocifensive responses in neuropathic pain.Neurobiology of disease · 2025Article
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.Molecular pharmacology · 2024Article
- BNST GluN2D-containing NMDARs contribute to ethanol intake but not negative affective behaviors in female mice.Alcohol, clinical & experimental research · 2024Article
- Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Riley E PerszykDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
John O DiRaddoDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Katie L StrongDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Chian-Ming LowDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Kevin K OgdenDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Alpa KhatriDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Geoffrey A VargishDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Kenneth A PelkeyDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Ludovic TricoireDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Dennis C LiottaDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Yoland SmithDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Chris J McBainDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland.
Stephen F TraynelisDepartments of Pharmacology (R.E.P., J.O.D., K.K.O., A.K., S.F.T.), Chemistry (J.O.D., K.L.S., D.C.L.), Neurology (Y.S.), Yerkes National Primate Research Center (Y.S.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (Y.S.), Emory University, Atlanta, Georgia; Departments of Pharmacology and Anaesthesiology (C.-M.L.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development (G.A.V., K.A.P., L.T., C.J.M.), National Institutes of Health, Bethesda, Maryland strayne@emory.edu.
Emory University · USNational Institutes of Health · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USNational University of Singapore · SG
Funding
Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0MCellular And Synaptic Physiology Of Hippocampal InterneuronsZIAHD001205 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MCBAIN, CHRIS J. · 2009 to 2025
$45.8MGraduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1MControl of Glutamate Receptor FunctionR01NS036654 · NINDS · EMORY UNIVERSITY · PI TRAYNELIS, STEPHEN F · 1998 to 2018
$3.7MMechanism of Action of Novel Subunit-Selective NMDA Receptor ModulatorsR01NS065371 · NINDS · EMORY UNIVERSITY · PI TRAYNELIS, STEPHEN F · 2009 to 2018
$3.4MNIGMS NIH HHS T32 GM008602NIH HHS P51 OD011132NINDS NIH HHS R01 NS036654NINDS NIH HHS R01 NS065371
Abstract
N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamatergic receptors that have been implicated in learning, development, and neuropathological conditions. They are typically composed of GluN1 and GluN2A-D subunits. Whereas a great deal is known about the role of GluN2A- and GluN2B-containing NMDARs, much less is known about GluN2D-containing NMDARs. Here we explore the subunit composition of synaptic NMDARs on hippocampal interneurons. GluN2D mRNA was detected by single-cell PCR and in situ hybridization in diverse interneuron subtypes in the CA1 region of the hippocampus. The GluN2D subunit was detectable by immunoblotting and immunohistochemistry in all subfields of the hippocampus in young and adult mice. In whole-cell patch-clamp recordings from acute hippocampal slices, (+)-CIQ, the active enantiomer of the positive allosteric modulator CIQ, significantly enhanced the amplitude of the NMDAR component of miniature excitatory postsynaptic currents (mEPSCs) in CA1 interneurons but not in pyramidal cells. (+)-CIQ had no effect in slices from Grin2d-/- mice, suggesting that GluN2D-containing NMDARs participate in excitatory synaptic transmission onto hippocampal interneurons. The time course of the NMDAR component of the mEPSC was unaffected by (+)-CIQ potentiation and was not accelerated in slices from Grin2d-/- mice compared with wild-type, suggesting that GluN2D does not detectably slow the NMDAR EPSC time course at this age. (+)-CIQ increased the activity of CA1 interneurons as detected by the rate and net charge transfer of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from CA1 pyramidal cells. These data provide evidence that interneurons contain synaptic NMDARs possessing a GluN2D subunit, which can influence interneuron function and signal processing.
Indexed as
Synaptic TransmissionAllosteric RegulationAnimalsCA1 Region, HippocampalExcitatory Postsynaptic PotentialsHippocampusInterneuronsIon Channel GatingIsoquinolinesMice, Inbred C57BLRatsReal-Time Polymerase Chain ReactionReceptors, N-Methyl-D-AspartateRNA, MessengerStereoisomerismTime Factors(6,7-dimethoxy-4-methylisoquinolinyl)-(4'-methoxyphenyl)methanoneIsoquinolinesNR2D NMDA receptorReceptors, N-Methyl-D-AspartateRNA, Messenger
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