Skip to main content
SpringerLink
Log in

NMDA receptor function: subunit composition versus spatial distribution

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

NMDA receptors (NMDARs) play a pivotal role in the regulation of neuronal communication and synaptic function in the central nervous system. The subunit composition and compartmental localization of NMDARs in neurons affect channel activity and downstream signaling. This review discusses the distinct NMDAR subtypes and their function at synaptic, perisynaptic, and extrasynaptic sites of excitatory and inhibitory neurons. Many neurons express more than one of the modulatory NR2 subunits that participate in the formation of di- and/or triheteromeric channel assemblies (e.g., NR1/NR2A, NR1/NR2B, and/or NR1/NR2A/NR2B). Depending on the subunit composition and presence or absence of intracellular binding partners along the postsynaptic membrane, these NMDAR subtypes are allocated to distinct synaptic inputs converging onto a neuron or are distributed differentially among synaptic or extrasynaptic sites. These sites can carry NR2A and NR2B subunits, supporting the hypothesis that the spatial distribution of scaffolding and signaling complexes critically determines the full spectrum of NMDAR signaling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Barth AL, Malenka RC (2001) NMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses. Nat Neurosci 4:235–236

    PubMed  CAS  Google Scholar 

  • Bayer KU, De Koninck P, Leonard AS, Hell JW, Schulman H (2001) Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 411:801–805

    PubMed  CAS  Google Scholar 

  • Berberich S, Punnakkal P, Jensen V, Pawlak V, Seeburg PH, Hvalby O, Köhr G (2005) Lack of NMDA receptor subtype selectivity for hippocampal long-term potentiation. J Neurosci 25:6907–6910

    PubMed  CAS  Google Scholar 

  • Binshtok AM, Fleidervish IA, Sprengel R, Gutnick MJ (2006) NMDA receptors in layer 4 spiny stellate cells of the mouse barrel cortex contain the NR2C subunit. J Neurosci 26:708–715

    PubMed  CAS  Google Scholar 

  • Brickley SG, Misra C, Mok MH, Mishina M, Cull-Candy SG (2003) NR2B and NR2D subunits coassemble in cerebellar Golgi cells to form a distinct NMDA receptor subtype restricted to extrasynaptic sites. J Neurosci 23:4958–4966

    PubMed  CAS  Google Scholar 

  • Carter AG, Regehr WG (2000) Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J Neurosci 20:4423–4434

    PubMed  CAS  Google Scholar 

  • Cathala L, Misra C, Cull-Candy S (2000) Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses. J Neurosci 20:5899–5905

    PubMed  CAS  Google Scholar 

  • Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S, Sevarino KA, Nakanishi N, Tong G, Lipton SA, Zhang D (2002) Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415:793–798

    PubMed  CAS  Google Scholar 

  • Chazot PL (2004) The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS pathologies. Curr Med Chem 11:389–396

    PubMed  CAS  Google Scholar 

  • Chen N, Moshaver A, Raymond LA (1997) Differential sensitivity of recombinant N-methyl-D-aspartate receptor subtypes to zinc inhibition. Mol Pharmacol 51:1015–1023

    PubMed  CAS  Google Scholar 

  • Chen PE, Wyllie DJ (2006) Pharmacological insights obtained from structure-function studies of ionotropic glutamate receptors. Br J Pharmacol 147:839–853

    PubMed  CAS  Google Scholar 

  • Chen S, Diamond JS (2002) Synaptically released glutamate activates extrasynaptic NMDA receptors on cells in the ganglion cell layer of rat retina. J Neurosci 22:2165–2173

    PubMed  CAS  Google Scholar 

  • Clark BA, Cull-Candy SG (2002) Activity-dependent recruitment of extrasynaptic NMDA receptor activation at an AMPA receptor-only synapse. J Neurosci 22:4428–4436

    PubMed  CAS  Google Scholar 

  • Collingridge GL, Isaac JT, Wang YT (2004) Receptor trafficking and synaptic plasticity. Nat Rev Neurosci 5:952–962

    PubMed  CAS  Google Scholar 

  • Cull-Candy SG, Leszkiewicz DN (2004) Role of distinct NMDA receptor subtypes at central synapses. Sci STKE 2004:re16

    PubMed  Google Scholar 

  • Dalby NO, Mody I (2003) Activation of NMDA receptors in rat dentate gyrus granule cells by spontaneous and evoked transmitter release. J Neurophysiol 90:786–797

    PubMed  CAS  Google Scholar 

  • Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61

    PubMed  CAS  Google Scholar 

  • Donevan SD, McCabe RT (2000) Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors. Mol Pharmacol 58:614–623

    PubMed  CAS  Google Scholar 

  • Faber ES, Delaney AJ, Sah P (2005) SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala. Nat Neurosci 8:635–641

    PubMed  CAS  Google Scholar 

  • Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43:729–743

    PubMed  CAS  Google Scholar 

  • Feng B, Tse HW, Skifter DA, Morley R, Jane DE, Monaghan DT (2004) Structure-activity analysis of a novel NR2C/NR2D-preferring NMDA receptor antagonist: 1-(phenanthrene-2-carbonyl) piperazine-2,3-dicarboxylic acid. Br J Pharmacol 141:508–516

    PubMed  CAS  Google Scholar 

  • Feng B, Morley RM, Jane DE, Monaghan DT (2005) The effect of competitive antagonist chain length on NMDA receptor subunit selectivity. Neuropharmacology 48:354–359

    PubMed  CAS  Google Scholar 

  • Fischer G, Mutel V, Trube G, Malherbe P, Kew JN, Mohacsi E, Heitz MP, Kemp JA (1997) Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther 283:1285–1292

    PubMed  CAS  Google Scholar 

  • Flint AC, Maisch US, Weishaupt JH, Kriegstein AR, Monyer H (1997) NR2A subunit expression shortens NMDA receptor synaptic currents in developing neocortex. J Neurosci 17:2469–2476

    PubMed  CAS  Google Scholar 

  • Fujisawa S, Aoki C (2003) In vivo blockade of N-methyl-D-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex. Neuroscience 121:51–63

    PubMed  CAS  Google Scholar 

  • Furukawa H, Singh SK, Mancusso R, Gouaux E (2005) Subunit arrangement and function in NMDA receptors. Nature 438:185–192

    PubMed  CAS  Google Scholar 

  • Goldberg JH, Yuste R, Tamas G (2003) Ca2+ imaging of mouse neocortical interneurone dendrites: contribution of Ca2+-permeable AMPA and NMDA receptors to subthreshold Ca2+ dynamics. J Physiol (Lond) 551:67–78

    CAS  Google Scholar 

  • Gotz T, Kraushaar U, Geiger J, Lubke J, Berger T, Jonas P (1997) Functional properties of AMPA and NMDA receptors expressed in identified types of basal ganglia neurons. J Neurosci 17:204–215

    PubMed  CAS  Google Scholar 

  • Hardingham GE, Fukunaga Y, Bading H (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 5:405–414

    PubMed  CAS  Google Scholar 

  • Hatton CJ, Paoletti P (2005) Modulation of triheteromeric NMDA receptors by N-terminal domain ligands. Neuron 46:261–274

    PubMed  CAS  Google Scholar 

  • Hayashi Y, Majewska AK (2005) Dendritic spine geometry: functional implication and regulation. Neuron 46:529–532

    PubMed  CAS  Google Scholar 

  • Huang YH, Bergles DE (2004) Glutamate transporters bring competition to the synapse. Curr Opin Neurobiol 14:346–352

    PubMed  CAS  Google Scholar 

  • Inoue A, Okabe S (2003) The dynamic organization of postsynaptic proteins: translocating molecules regulate synaptic function. Curr Opin Neurobiol 13:332–340

    PubMed  CAS  Google Scholar 

  • Isaacson JS, Murphy GJ (2001) Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to Ca2+-activated K+ channels. Neuron 31:1027–1034

    PubMed  CAS  Google Scholar 

  • Ito I, Futai K, Katagiri H, Watanabe M, Sakimura K, Mishina M, Sugiyama H (1997) Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon 1 or epsilon 2 subunit. J Physiol (Lond) 500:401–408

    CAS  Google Scholar 

  • Ivanov A, Pellegrino C, Rama S, Dumalska I, Salyha Y, Ben-Ari Y, Medina I (2006) Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the ERK activity in cultured rat hippocampal neurons. J Physiol (Lond) 572:789–798

    CAS  Google Scholar 

  • Janssen WG, Vissavajjhala P, Andrews G, Moran T, Hof PR, Morrison JH (2005) Cellular and synaptic distribution of NR2A and NR2B in macaque monkey and rat hippocampus as visualized with subunit-specific monoclonal antibodies. Exp Neurol 191 (Suppl 1):S28–S44

    PubMed  CAS  Google Scholar 

  • Jones S, Gibb AJ (2005) Functional NR2B- and NR2D-containing NMDA receptor channels in rat substantia nigra dopaminergic neurones. J Physiol (Lond) 569:209–221

    CAS  Google Scholar 

  • Karadottir R, Cavelier P, Bergersen LH, Attwell D (2005) NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438:1162–1166

    PubMed  CAS  Google Scholar 

  • Kawakami R, Shinohara Y, Kato Y, Sugiyama H, Shigemoto R, Ito I (2003) Asymmetrical allocation of NMDA receptor epsilon2 subunits in hippocampal circuitry. Science 300:990–994

    PubMed  CAS  Google Scholar 

  • Kew JN, Trube G, Kemp JA (1996) A novel mechanism of activity-dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones. J Physiol (Lond) 497:761–772

    CAS  Google Scholar 

  • Kim MJ, Dunah AW, Wang YT, Sheng M (2005) Differential roles of NR2A-and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Neuron 46:745–760

    PubMed  CAS  Google Scholar 

  • Kinney JW, Davis CN, Tabarean I, Conti B, Bartfai T, Behrens MM (2006) A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J Neurosci 26:1604–1615

    PubMed  CAS  Google Scholar 

  • Kirson ED, Yaari Y (1996) Synaptic NMDA receptors in developing mouse hippocampal neurones: functional properties and sensitivity to ifenprodil. J Physiol (Lond) 497:437–455

    CAS  Google Scholar 

  • Kiyama Y, Manabe T, Sakimura K, Kawakami F, Mori H, Mishina M (1998) Increased thresholds for long-term potentiation and contextual learning in mice lacking the NMDA-type glutamate receptor epsilon1 subunit. J Neurosci 18:6704–6712

    PubMed  CAS  Google Scholar 

  • Klein RC, Prorok M, Galdzicki Z, Castellino FJ (2001) The amino acid residue at sequence position 5 in the conantokin peptides partially governs subunit-selective antagonism of recombinant N-methyl-D-aspartate receptors. J Biol Chem 276:26860–26867

    PubMed  CAS  Google Scholar 

  • Köhr G, Jensen V, Koester HJ, Mihaljevic AL, Utvik JK, Kvello A, Ottersen OP, Seeburg PH, Sprengel R, Hvalby O (2003) Intracellular domains of NMDA receptor subtypes are determinants for long-term potentiation induction. J Neurosci 23:10791–10799

    PubMed  Google Scholar 

  • Krapivinsky G, Krapivinsky L, Manasian Y, Ivanov A, Tyzio R, Pellegrino C, Ben-Ari Y, Clapham DE, Medina I (2003) The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron 40:775–784

    PubMed  CAS  Google Scholar 

  • Kullmann DM, Asztely F (1998) Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Trends Neurosci 21:8–14

    PubMed  CAS  Google Scholar 

  • Kumar SS, Huguenard JR (2003) Pathway-specific differences in subunit composition of synaptic NMDA receptors on pyramidal neurons in neocortex. J Neurosci 23:10074–10083

    PubMed  CAS  Google Scholar 

  • Lalo U, Pankratov Y, Kirchhoff F, North RA, Verkhratsky A (2006) NMDA receptors mediate neuron-to-glia signaling in mouse cortical astrocytes. J Neurosci 26:2673–2683

    PubMed  CAS  Google Scholar 

  • Lee FJ, Xue S, Pei L, Vukusic B, Chery N, Wang Y, Wang YT, Niznik HB, Yu XM, Liu F (2002) Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell 111:219–230

    PubMed  CAS  Google Scholar 

  • Lei S, McBain CJ (2002) Distinct NMDA receptors provide differential modes of transmission at mossy fiber-interneuron synapses. Neuron 33:921–933

    PubMed  CAS  Google Scholar 

  • Li B, Chen N, Luo T, Otsu Y, Murphy TH, Raymond LA (2002) Differential regulation of synaptic and extra-synaptic NMDA receptors. Nat Neurosci 5:833–834

    PubMed  CAS  Google Scholar 

  • Li B, Otsu Y, Murphy TH, Raymond LA (2003) Developmental decrease in NMDA receptor desensitization associated with shift to synapse and interaction with postsynaptic density-95. J Neurosci 23:11244–11254

    PubMed  CAS  Google Scholar 

  • Li JH, Wang YH, Wolfe BB, Krueger KE, Corsi L, Stocca G, Vicini S (1998) Developmental changes in localization of NMDA receptor subunits in primary cultures of cortical neurons. Eur J Neurosci 10:1704–1715

    PubMed  CAS  Google Scholar 

  • Li S, Tian X, Hartley DM, Feig LA (2006) Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression. J Neurosci 26:1721–1729

    PubMed  CAS  Google Scholar 

  • Liu L, Wong TP, Pozza MF, Lingenhoehl K, Wang Y, Sheng M, Auberson YP, Wang YT (2004) Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science 304:1021–1024

    PubMed  CAS  Google Scholar 

  • Lopez de Armentia M, Sah P (2003) Development and subunit composition of synaptic NMDA receptors in the amygdala: NR2B synapses in the adult central amygdala. J Neurosci 23:6876–6883

    PubMed  CAS  Google Scholar 

  • Lozovaya NA, Grebenyuk SE, Tsintsadze T, Feng B, Monaghan DT, Krishtal OA (2004) Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape “superslow” afterburst EPSC in rat hippocampus. J Physiol (Lond) 558:451–463

    CAS  Google Scholar 

  • Lu HC, Gonzalez E, Crair MC (2001) Barrel cortex critical period plasticity is independent of changes in NMDA receptor subunit composition. Neuron 32:619–634

    PubMed  Google Scholar 

  • Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21

    PubMed  CAS  Google Scholar 

  • Massey PV, Johnson BE, Moult PR, Auberson YP, Brown MW, Molnar E, Collingridge GL, Bashir ZI (2004) Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci 24:7821–7828

    PubMed  CAS  Google Scholar 

  • Mohrmann R, Köhr G, Hatt H, Sprengel R, Gottmann K (2002) Deletion of the C-terminal domain of the NR2B subunit alters channel properties and synaptic targeting of N-methyl-D-aspartate receptors in nascent neocortical synapses. J Neurosci Res 68:265–275

    PubMed  CAS  Google Scholar 

  • Momiyama A (2000) Distinct synaptic and extrasynaptic NMDA receptors identified in dorsal horn neurones of the adult rat spinal cord. J Physiol (Lond) 523:621–628

    CAS  Google Scholar 

  • Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529–540

    PubMed  CAS  Google Scholar 

  • Mott DD, Doherty JJ, Zhang S, Washburn MS, Fendley MJ, Lyuboslavsky P, Traynelis SF, Dingledine R (1998) Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition. Nat Neurosci 1:659–667

    PubMed  CAS  Google Scholar 

  • Nagy J, Horvath C, Farkas S, Kolok S, Szombathelyi Z (2004) NR2B subunit selective NMDA antagonists inhibit neurotoxic effect of alcohol-withdrawal in primary cultures of rat coritcal neurones. Neurochem Int 44:17–23

    PubMed  CAS  Google Scholar 

  • Nakazawa K, McHugh TJ, Wilson MA, Tonegawa S (2004) NMDA receptors, place cells and hippocampal spatial memory. Nat Rev Neurosci 5:361–372

    PubMed  CAS  Google Scholar 

  • Neyton J, Paoletti P (2006) Relating NMDA receptor function to receptor subunit composition: limitations of the pharmacological approach. J Neurosci 26:1331–1333

    PubMed  CAS  Google Scholar 

  • Ngo-Anh TJ, Bloodgood BL, Lin M, Sabatini BL, Maylie J, Adelman JP (2005) SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines. Nat Neurosci 8:642–649

    PubMed  CAS  Google Scholar 

  • Nong Y, Huang YQ, Salter MW (2004) NMDA receptors are movin′ in. Curr Opin Neurobiol 14:353–361

    PubMed  CAS  Google Scholar 

  • Paoletti P, Ascher P, Neyton J (1997) High-affinity zinc inhibition of NMDA NR1-NR2A receptors. J Neurosci 17:5711–5725

    PubMed  CAS  Google Scholar 

  • Perez-Otano I, Ehlers MD (2005) Homeostatic plasticity and NMDA receptor trafficking. Trends Neurosci 28:229–238

    PubMed  CAS  Google Scholar 

  • Perez-Otano I, Schulteis CT, Contractor A, Lipton SA, Trimmer JS, Sucher NJ, Heinemann SF (2001) Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. J Neurosci 21:1228–1237

    PubMed  CAS  Google Scholar 

  • Pinheiro P, Mulle C (2006) Kainate receptors. Cell Tissue Res (DOI: 10.1007/s00441-006-0265-6; this issue)

  • Prybylowski K, Wenthold RJ (2004) N-methyl-D-aspartate receptors: subunit assembly and trafficking to the synapse. J Biol Chem 279:9673–9676

    PubMed  CAS  Google Scholar 

  • Roche KW, Standley S, McCallum J, Dune Ly C, Ehlers MD, Wenthold RJ (2001) Molecular determinants of NMDA receptor internalization. Nat Neurosci 4:794–802

    PubMed  CAS  Google Scholar 

  • Rumbaugh G, Vicini S (1999) Distinct synaptic and extrasynaptic NMDA receptors in developing cerebellar granule neurons. J Neurosci 19:10603–10610

    PubMed  CAS  Google Scholar 

  • Salter MG, Fern R (2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438:1167–1171

    PubMed  CAS  Google Scholar 

  • Sattler R, Xiong Z, Lu WY, MacDonald JF, Tymianski M (2000) Distinct roles of synaptic and extrasynaptic NMDA receptors in excitotoxicity. J Neurosci 20:22–33

    PubMed  CAS  Google Scholar 

  • Scimemi A, Fine A, Kullmann DM, Rusakov DA (2004) NR2B-containing receptors mediate cross talk among hippocampal synapses. J Neurosci 24:4767–4777

    PubMed  CAS  Google Scholar 

  • Sheng M, Kim MJ (2002) Postsynaptic signaling and plasticity mechanisms. Science 298:776–780

    PubMed  CAS  Google Scholar 

  • Sinor JD, Du S, Venneti S, Blitzblau RC, Leszkiewicz DN, Rosenberg PA, Aizenman E (2000) NMDA and glutamate evoke excitotoxicity at distinct cellular locations in rat cortical neurons in vitro. J Neurosci 20:8831–8837

    PubMed  CAS  Google Scholar 

  • Sprengel R (2006) Glutamate receptors: AMPAR. Cell Tissue Res (this issue)

  • Standaert DG, Landwehrmeyer GB, Kerner JA, Penney JB Jr, Young AB (1996) Expression of NMDAR2D glutamate receptor subunit mRNA in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus. Brain Res Mol Brain Res 42:89–102

    PubMed  CAS  Google Scholar 

  • Steigerwald F, Schulz TW, Schenker LT, Kennedy MB, Seeburg PH, Köhr G (2000) C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors. J Neurosci 20:4573–4581

    PubMed  CAS  Google Scholar 

  • Stocca G, Vicini S (1998) Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons. J Physiol (Lond) 507:13–24

    CAS  Google Scholar 

  • Szinyei C, Stork O, Pape HC (2003) Contribution of NR2B subunits to synaptic transmission in amygdaloid interneurons. J Neurosci 23:2549–2556

    PubMed  CAS  Google Scholar 

  • Takahashi T, Feldmeyer D, Suzuki N, Onodera K, Cull CS, Sakimura K, Mishina M (1996) Functional correlation of NMDA receptor epsilon subunits expression with the properties of single-channel and synaptic currents in the developing cerebellum. J Neurosci 16:4376–4382

    PubMed  CAS  Google Scholar 

  • Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ (1999) Genetic enhancement of learning and memory in mice. Nature 401:63–69

    PubMed  CAS  Google Scholar 

  • Thomas CG, Miller AJ, Westbrook GL (2006) Synaptic and extrasynaptic NMDA receptor NR2 subunits in cultured hippocampal neurons. J Neurophysiol 95:1727–1734

    PubMed  CAS  Google Scholar 

  • Tovar KR, Westbrook GL (1999) The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J Neurosci 19:4180–4188

    PubMed  CAS  Google Scholar 

  • Tovar KR, Westbrook GL (2002) Mobile NMDA receptors at hippocampal synapses. Neuron 34:255–264

    PubMed  CAS  Google Scholar 

  • Traynelis SF, Burgess MF, Zheng F, Lyuboslavsky P, Powers JL (1998) Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit. J Neurosci 18:6163–6175

    PubMed  CAS  Google Scholar 

  • Triller A, Choquet D (2005) Surface trafficking of receptors between synaptic and extrasynaptic membranes: and yet they do move! Trends Neurosci 28:133–139

    PubMed  CAS  Google Scholar 

  • Tzingounis AV, Nicoll RA (2004) Presynaptic NMDA receptors get into the act. Nat Neurosci 7:419–420

    PubMed  CAS  Google Scholar 

  • Ullian EM, Barkis WB, Chen S, Diamond JS, Barres BA (2004) Invulnerability of retinal ganglion cells to NMDA excitotoxicity. Mol Cell Neurosci 26:544–557

    PubMed  CAS  Google Scholar 

  • Vanhoutte P, Bading H (2003) Opposing roles of synaptic and extrasynaptic NMDA receptors in neuronal calcium signalling and BDNF gene regulation. Curr Opin Neurobiol 13:366–371

    PubMed  CAS  Google Scholar 

  • Watanabe M, Mishina M, Inoue Y (1994) Distinct spatiotemporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum. J Comp Neurol 343:513–559

    PubMed  CAS  Google Scholar 

  • Weitlauf C, Honse Y, Auberson YP, Mishina M, Lovinger DM, Winder DG (2005) Activation of NR2A-containing NMDA receptors is not obligatory for NMDA receptor-dependent long-term potentiation. J Neurosci 25:8386–8390

    PubMed  CAS  Google Scholar 

  • Williams K (1993) Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol 44:851–859

    PubMed  CAS  Google Scholar 

  • Wittekindt B, Malany S, Schemm R, Otvos L, Maccecchini ML, Laube B, Betz H (2001) Point mutations identify the glutamate binding pocket of the N-methyl-D-aspartate receptor as major site of conantokin-G inhibition. Neuropharmacology 41:753–761

    PubMed  CAS  Google Scholar 

  • Wong RW, Setou M, Teng J, Takei Y, Hirokawa N (2002) Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice. Proc Natl Acad Sci USA 99:14500–14505

    PubMed  CAS  Google Scholar 

  • Wu Y, Kawakami R, Shinohara Y, Fukaya M, Sakimura K, Mishina M, Watanabe M, Ito I, Shigemoto R (2005) Target-cell-specific left-right asymmetry of NMDA receptor content in Schaffer collateral synapses in epsilon1/NR2A knock-out mice. J Neurosci 25:9213–9226

    PubMed  CAS  Google Scholar 

  • Zhao MG, Toyoda H, Lee YS, Wu LJ, Ko SW, Zhang XH, Jia Y, Shum F, Xu H, Li BM, Kaang BK, Zhuo M (2005) Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 47:859–872

    PubMed  CAS  Google Scholar 

  • Zundert B van, Yoshii A, Constantine-Paton M (2004) Receptor compartmentalization and trafficking at glutamate synapses: a developmental proposal. Trends Neurosci 27:428–437

    PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks Simone Astori and Drs. Pavel Osten, Peter H. Seeburg, and Rolf Sprengel for critically reading this review.

Author information

Authors and Affiliations

  1. Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany

    Georg Köhr

Authors
  1. Georg Köhr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georg Köhr.

Additional information

The author thanks the Deutsche Forschungsgemeinschaft for financial support (Ko 1064/5).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Köhr, G. NMDA receptor function: subunit composition versus spatial distribution. Cell Tissue Res 326, 439–446 (2006). https://doi.org/10.1007/s00441-006-0273-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0273-6

Keywords

Search

Navigation