Home LiteratureArticle Details
PMID: 19192303 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

Plasticity of NMDA receptor NR2B subunit in memory and chronic pain.

Molecular brain ·Vol. 2 ·2009-02-03 ·Pages 4

Zhuo M

Abstract

Glutamatergic synapses play critical roles in brain functions and diseases. Long-term potentiation (LTP) is a most effective cellular model for investigating the synaptic changes that underlie learning as well as brain disease--although different molecular mechanisms are likely involved in LTP in physiological and pathological conditions. In the case of learning, N-methyl-D-aspartate (NMDA) receptor is known to be important for triggering learning-related plasticity; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptors are thought to be important for the expression of synaptic changes. In this review, I will examine recent evidence on the novel roles of NMDA receptors, in particular NR2B subunit-containing NMDA receptors in learning and chronic pain. A positive feedback control of NR2B receptor subunit is proposed to explain cortical sensitization involved in chronic pain, but not learning and memory.

MeSH Terms
Animals Chronic Disease Humans Memory/physiology Neuronal Plasticity/physiology Pain/physiopathology Protein Subunits/metabolism Receptors, N-Methyl-D-Aspartate/metabolism
Chemicals
NR2B NMDA receptor Protein Subunits Receptors, N-Methyl-D-Aspartate
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Zhuo Min
Department of Physiology, Faculty of Medicine, University of Toronto Centre for the Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. [email protected]
References (48)
48 references, click to expand
  1. NMDA receptor-dependent ocular dominance plasticity in adult visual cortex.
    Neuron. 2003 Jun 19;38(6):977-85 PMID: 12818182
  2. Involvement of NR2A- or NR2B-containing N-methyl-D-aspartate receptors in the potentiation of cortical layer 5 pyramidal neurone inputs depends on the developmental stage.
    Eur J Neurosci. 2007 Jul;26(2):289-301 PMID: 17650107
  3. Time-dependent postsynaptic AMPA GluR1 receptor recruitment in the cingulate synaptic potentiation.
    Dev Neurobiol. 2007 Mar;67(4):498-509 PMID: 17443804
  4. Mechanism of partial agonism at NMDA receptors for a conformationally restricted glutamate analog.
    J Neurosci. 2005 Aug 24;25(34):7858-66 PMID: 16120788
  5. Glutamate uptake determines pathway specificity of long-term potentiation in the neural circuitry of fear conditioning.
    Neuron. 2004 Jan 8;41(1):139-51 PMID: 14715141
  6. Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice.
    J Neurosci. 2005 Jan 26;25(4):977-84 PMID: 15673679
  7. AMPA receptor trafficking and synaptic plasticity.
    Annu Rev Neurosci. 2002;25:103-26 PMID: 12052905
  8. Molecular dissection of hippocampal theta-burst pairing potentiation.
    Proc Natl Acad Sci U S A. 2002 May 28;99(11):7740-5 PMID: 12032353
  9. Synaptic amplifier of inflammatory pain in the spinal dorsal horn.
    Science. 2006 Jun 16;312(5780):1659-62 PMID: 16778058
  10. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport.
    Science. 2000 Jun 9;288(5472):1796-802 PMID: 10846156
  11. Calcium-stimulated adenylyl cyclases required for long-term potentiation in the anterior cingulate cortex.
    J Neurophysiol. 2005 Jul;94(1):878-82 PMID: 15985698
  12. The effect of (+/-)-CP-101,606, an NMDA receptor NR2B subunit selective antagonist, in the Morris watermaze.
    Eur J Pharmacol. 2003 Aug 29;476(3):193-9 PMID: 12969766
  13. Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice.
    Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14500-5 PMID: 12391294
  14. The role of NMDAR subtypes and charge transfer during hippocampal LTP induction.
    Neuropharmacology. 2007 Jan;52(1):77-86 PMID: 16901514
  15. Calcium calmodulin-stimulated adenylyl cyclases contribute to activation of extracellular signal-regulated kinase in spinal dorsal horn neurons in adult rats and mice.
    J Neurosci. 2006 Jan 18;26(3):851-61 PMID: 16421305
  16. The glutamate receptor ion channels.
    Pharmacol Rev. 1999 Mar;51(1):7-61 PMID: 10049997
  17. A synaptic model of memory: long-term potentiation in the hippocampus.
    Nature. 1993 Jan 7;361(6407):31-9 PMID: 8421494
  18. Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory.
    Neuropharmacology. 2007 Jan;52(1):215-27 PMID: 16919687
  19. Two forms of synaptic plasticity with distinct dependence on age, experience, and NMDA receptor subtype in rat visual cortex.
    J Neurosci. 2003 Jul 23;23(16):6557-66 PMID: 12878697
  20. Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors.
    J Neurophysiol. 1998 Feb;79(2):555-66 PMID: 9463421
  21. Long-term potentiation--a decade of progress?
    Science. 1999 Sep 17;285(5435):1870-4 PMID: 10489359
  22. Disruption of AMPA receptor endocytosis impairs the extinction, but not acquisition of learned fear.
    Neuropsychopharmacology. 2008 Sep;33(10):2416-26 PMID: 18046303
  23. Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases.
    Neuron. 2002 Nov 14;36(4):713-26 PMID: 12441059
  24. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression.
    Nat Neurosci. 2001 Feb;4(2):164-9 PMID: 11175877
  25. Dark-rearing decreases NR2A N-methyl-D-aspartate receptor subunit in all visual cortical layers.
    Neuroscience. 2003;119(4):1013-22 PMID: 12831860
  26. On the respective roles of nitric oxide and carbon monoxide in long-term potentiation in the hippocampus.
    Learn Mem. 1999 Jan-Feb;6(1):63-76 PMID: 10355525
  27. Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning.
    J Neurosci. 2001 Sep 1;21(17):6889-96 PMID: 11517276
  28. Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex.
    Neuron. 2001 Jan;29(1):157-69 PMID: 11182088
  29. Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex.
    J Neurosci. 2008 Jul 16;28(29):7445-53 PMID: 18632948
  30. NMDA receptor subunits: diversity, development and disease.
    Curr Opin Neurobiol. 2001 Jun;11(3):327-35 PMID: 11399431
  31. Cortical excitation and chronic pain.
    Trends Neurosci. 2008 Apr;31(4):199-207 PMID: 18329111
  32. NMDA currents and receptor protein are downregulated in the amygdala during maintenance of fear memory.
    J Neurosci. 2003 Nov 12;23(32):10283-91 PMID: 14614087
  33. Conditioning-strength dependent involvement of NMDA NR2B subtype receptor in the basolateral nucleus of amygdala in acquisition of auditory fear memory.
    Neuropharmacology. 2008 Aug;55(2):238-46 PMID: 18573264
  34. NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala.
    J Neurosci. 2002 Jun 15;22(12):5239-49 PMID: 12077219
  35. Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: the role of voltage-dependent Ca2+ channels in the induction of LTP.
    J Neurosci. 1993 Feb;13(2):568-76 PMID: 8381168
  36. The molecular biology of memory storage: a dialogue between genes and synapses.
    Science. 2001 Nov 2;294(5544):1030-8 PMID: 11691980
  37. Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation.
    J Neurosci. 2005 Nov 30;25(48):11107-16 PMID: 16319310
  38. Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNS.
    J Physiol. 2008 May 15;586(10):2539-50 PMID: 18372311
  39. Molecular mechanisms underlying emotional learning and memory in the lateral amygdala.
    Neuron. 2004 Sep 30;44(1):75-91 PMID: 15450161
  40. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia.
    Science. 2003 Feb 21;299(5610):1237-40 PMID: 12595694
  41. Genetic enhancement of learning and memory in mice.
    Nature. 1999 Sep 2;401(6748):63-9 PMID: 10485705
  42. KIF17 dynamics and regulation of NR2B trafficking in hippocampal neurons.
    J Neurosci. 2003 Jan 1;23(1):131-40 PMID: 12514209
  43. Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression.
    J Neurosci. 2004 Sep 8;24(36):7821-8 PMID: 15356193
  44. Two components of long-term potentiation induced by different patterns of afferent activation.
    Nature. 1990 Oct 4;347(6292):477-9 PMID: 1977084
  45. Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity.
    Science. 2004 May 14;304(5673):1021-4 PMID: 15143284
  46. A hippocampal NR2B deficit can mimic age-related changes in long-term potentiation and spatial learning in the Fischer 344 rat.
    J Neurosci. 2002 May 1;22(9):3628-37 PMID: 11978838
  47. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory.
    Neuron. 2005 Sep 15;47(6):859-72 PMID: 16157280
  48. Amygdala infusions of an NR2B-selective or an NR2A-preferring NMDA receptor antagonist differentially influence fear conditioning and expression in the fear-potentiated startle test.
    Learn Mem. 2008 Jan 28;15(2):67-74 PMID: 18230675
Article Info
Journal
Molecular brain
Abbr.
Mol Brain
ISSN
1756-6606
DOI
10.1186/1756-6606-2-4
Email
[email protected]
Published
2009-02-03
Epub
2009-00-03
Pages
4
Language
English
Region
England
NLM ID
101468876
PMCID
PMC2644299
Subset
IM
Grants
Canadian Institutes of Health Research · 84256 · Canada
Canadian Institutes of Health Research · CIHR81086 · Canada
External Links
PubMed source DOI: 10.1186/1756-6606-2-4 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2