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Mol Pharmacol
2016 Dec 13;906:689-702. doi: 10.1124/mol.116.105130.
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GluN2D-Containing N-methyl-d-Aspartate Receptors Mediate Synaptic Transmission in Hippocampal Interneurons and Regulate Interneuron Activity.
Perszyk RE, DiRaddo JO, Strong KL, Low CM, Ogden KK, Khatri A, Vargish GA, Pelkey KA, Tricoire L, Liotta DC, Smith Y, McBain CJ, Traynelis SF.
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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.
Akazawa,
Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats.
1994, Pubmed
Akazawa,
Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats.
1994,
Pubmed Bachtiar,
The role of inhibition in human motor cortical plasticity.
2014,
Pubmed Besnard,
Automated design of ligands to polypharmacological profiles.
2012,
Pubmed Cauli,
Molecular and physiological diversity of cortical nonpyramidal cells.
1997,
Pubmed Cauli,
Classification of fusiform neocortical interneurons based on unsupervised clustering.
2000,
Pubmed Choi,
Excitotoxic cell death.
1992,
Pubmed Clarke,
NMDA receptor NR2 subunit dependence of the slow component of magnesium unblock.
2006,
Pubmed Collingridge,
The NMDA receptor as a target for cognitive enhancement.
2013,
Pubmed Coyle,
NMDA receptor and schizophrenia: a brief history.
2012,
Pubmed Coyle,
Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia.
2003,
Pubmed Edman,
TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner.
2012,
Pubmed
,
Xenbase Hallett,
Rationale for and use of NMDA receptor antagonists in Parkinson's disease.
2004,
Pubmed Hansen,
Structural determinants of agonist efficacy at the glutamate binding site of N-methyl-D-aspartate receptors.
2013,
Pubmed
,
Xenbase Hansen,
Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors.
2014,
Pubmed
,
Xenbase Hao,
Depolarization gates spine calcium transients and spike-timing-dependent potentiation.
2012,
Pubmed Hildebrand,
GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord.
2014,
Pubmed Kew,
An allosteric interaction between the NMDA receptor polyamine and ifenprodil sites in rat cultured cortical neurones.
1998,
Pubmed Kullmann,
Long-term synaptic plasticity in hippocampal interneurons.
2007,
Pubmed Lacaille,
Local circuit interactions between oriens/alveus interneurons and CA1 pyramidal cells in hippocampal slices: electrophysiology and morphology.
1987,
Pubmed Lambolez,
AMPA receptor subunits expressed by single Purkinje cells.
1992,
Pubmed Landwehrmeyer,
NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum.
1995,
Pubmed Lester,
Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents.
1990,
Pubmed Liu,
Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses during early postnatal development.
2004,
Pubmed Lu,
Eye opening rapidly induces synaptic potentiation and refinement.
2004,
Pubmed Matta,
Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity.
2013,
Pubmed McBain,
Heterogeneity of synaptic glutamate receptors on CA3 stratum radiatum interneurones of rat hippocampus.
1993,
Pubmed McKay,
Direct pharmacological monitoring of the developmental switch in NMDA receptor subunit composition using TCN 213, a GluN2A-selective, glycine-dependent antagonist.
2012,
Pubmed
,
Xenbase Monyer,
Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.
1994,
Pubmed Mullasseril,
A subunit-selective potentiator of NR2C- and NR2D-containing NMDA receptors.
2010,
Pubmed Palmer,
Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.
2001,
Pubmed Paoletti,
Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mg2+.
1995,
Pubmed
,
Xenbase Pelkey,
mGluR7 is a metaplastic switch controlling bidirectional plasticity of feedforward inhibition.
2005,
Pubmed Pelkey,
Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons.
2015,
Pubmed Pelkey,
Compartmentalized Ca(2+) channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity.
2006,
Pubmed Porter,
Properties of bipolar VIPergic interneurons and their excitation by pyramidal neurons in the rat neocortex.
1998,
Pubmed Preskorn,
An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder.
2008,
Pubmed Preskorn,
Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent.
2015,
Pubmed Rudolf,
Expression of N-methyl-D-aspartate glutamate receptor subunits in the prefrontal cortex of the rat.
1996,
Pubmed Santangelo Freel,
Correction to Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-Based Potentiators of GluN2C and GluN2D Containing N-Methyl-d-aspartate Receptors.
2014,
Pubmed Santangelo Freel,
Synthesis and structure activity relationship of tetrahydroisoquinoline-based potentiators of GluN2C and GluN2D containing N-methyl-D-aspartate receptors.
2013,
Pubmed
,
Xenbase Siegler Retchless,
A single GluN2 subunit residue controls NMDA receptor channel properties via intersubunit interaction.
2012,
Pubmed Standaert,
Organization of N-methyl-D-aspartate glutamate receptor gene expression in the basal ganglia of the rat.
1994,
Pubmed Standaert,
Expression of NMDAR2D glutamate receptor subunit mRNA in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus.
1996,
Pubmed Stefanescu,
NMDA Receptors Mediate Stimulus-Timing-Dependent Plasticity and Neural Synchrony in the Dorsal Cochlear Nucleus.
2015,
Pubmed Swanger,
NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus.
2015,
Pubmed Sweatt,
Neural plasticity and behavior - sixty years of conceptual advances.
2016,
Pubmed Talaei,
Postnatal development and sensory experience synergistically underlie the excitatory/inhibitory features of hippocampal neural circuits: Glutamatergic and GABAergic neurotransmission.
2016,
Pubmed Thompson,
Immunohistochemical localization of N-methyl-D-aspartate receptor subunits in the adult murine hippocampal formation: evidence for a unique role of the NR2D subunit.
2002,
Pubmed Traynelis,
Glutamate receptor ion channels: structure, regulation, and function.
2010,
Pubmed Vance,
Modal gating of GluN1/GluN2D NMDA receptors.
2013,
Pubmed Vance,
GluN1 splice variant control of GluN1/GluN2D NMDA receptors.
2012,
Pubmed
,
Xenbase Verhoog,
Mechanisms underlying the rules for associative plasticity at adult human neocortical synapses.
2013,
Pubmed Vicini,
Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors.
1998,
Pubmed von Engelhardt,
GluN2D-containing NMDA receptors-mediate synaptic currents in hippocampal interneurons and pyramidal cells in juvenile mice.
2015,
Pubmed Wyllie,
Influence of GluN2 subunit identity on NMDA receptor function.
2013,
Pubmed Xue,
NMDA receptor activation enhances inhibitory GABAergic transmission onto hippocampal pyramidal neurons via presynaptic and postsynaptic mechanisms.
2011,
Pubmed Yuan,
Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.
2015,
Pubmed
