Home LiteratureArticle Details
PMID: 8816822 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Long-term potentiation increases tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit 2B in rat dentate gyrus in vivo.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 19 ·1996-09-17 ·Pages 10457-60

Rosenblum K, Dudai Y, Richter-Levin G

Abstract

Long-term potentiation (LTP) is a form of synaptic memory that may subserve developmental and behavioral plasticity. An intensively investigated form of LTP is dependent upon N-methyl-D-aspartate (NMDA) receptors and can be elicited in the dentate gyrus and hippocampal CA1. Induction of this type of LTP is triggered by influx of Ca2+ through activated NMDA receptors, but the downstream mechanisms of induction, and even more so of LTP maintenance, remain controversial. It has been reported that the function of NMDA receptor channel can be regulated by protein tyrosine kinases and protein phosphatases and that inhibition of protein tyrosine kinases impairs induction of LTP. Herein we report that LTP in the dentate gyrus is specifically correlated with tyrosine phosphorylation of the NMDA receptor subunit 2B in an NMDA receptor-dependent manner. The effect is observed with a delay of several minutes after LTP induction and persists in vivo for several hours. The potential relevance of this post-translational modification to mechanisms of LTP and circuit plasticity is discussed.

MeSH Terms
Amino Acid Sequence Animals Antibodies Dentate Gyrus/physiology Hippocampus/physiology Kinetics Long-Term Potentiation Male Molecular Sequence Data Peptide Fragments/chemistry,immunology Phosphorylation Phosphotyrosine/analysis Prosencephalon/physiology Pyramidal Cells/physiology Rats Rats, Wistar Receptors, N-Methyl-D-Aspartate/metabolism,physiology Synapses/physiology Time Factors
Chemicals
Antibodies Peptide Fragments Receptors, N-Methyl-D-Aspartate Phosphotyrosine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rosenblum K
Department of Neurobiology, Weizmann Institute of Science, Rehovot Israel.
Dudai Y
Richter-Levin G
References (37)
37 references, click to expand
  1. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory.
    Proc Natl Acad Sci U S A. 1989 Dec;86(23):9574-8 PMID: 2556718
  2. Long-lasting potentiation and epileptiform activity produced by GABAB receptor activation in the dentate gyrus of rat hippocampal slice.
    J Neurosci. 1991 May;11(5):1198-209 PMID: 1851214
  3. Persistent activation of cAMP-dependent protein kinase by regulated proteolysis suggests a neuron-specific function of the ubiquitin system in Aplysia.
    J Neurosci. 1995 Nov;15(11):7592-603 PMID: 7472510
  4. Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits.
    J Biol Chem. 1993 Feb 5;268(4):2836-43 PMID: 8428958
  5. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  6. Contributions of quisqualate and NMDA receptors to the induction and expression of LTP.
    Science. 1988 Dec 23;242(4886):1694-7 PMID: 2904701
  7. Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.
    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1157-61 PMID: 7862652
  8. Pharmacological evidence for a role of long-term potentiation in memory.
    FASEB J. 1994 Nov;8(14):1139-45 PMID: 7958619
  9. NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain.
    Biochem Biophys Res Commun. 1995 Nov 13;216(2):582-8 PMID: 7488151
  10. Structure and function of the NMDA receptor channel.
    Neuropharmacology. 1995 Oct;34(10):1219-37 PMID: 8570021
  11. Contrasting properties of two forms of long-term potentiation in the hippocampus.
    Nature. 1995 Sep 14;377(6545):115-8 PMID: 7675078
  12. Tyrosine kinase inhibitors, herbimycin A and lavendustin A, block formation of long-term potentiation in the dentate gyrus in vivo.
    Brain Res. 1993 Sep 3;621(1):167-70 PMID: 8221070
  13. Enhanced tyrosine phosphorylation of the 2B subunit of the N-methyl-D-aspartate receptor in long-term potentiation.
    Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10452-6 PMID: 8816821
  14. Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors.
    Nature. 1991 Oct 10;353(6344):558-60 PMID: 1656271
  15. The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior.
    J Neurosci. 1991 Jun;11(6):1585-96 PMID: 1646296
  16. A synaptic model of memory: long-term potentiation in the hippocampus.
    Nature. 1993 Jan 7;361(6407):31-9 PMID: 8421494
  17. Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by D(-)aminophosphonovalerate.
    Neuroscience. 1987 Jan;20(1):279-84 PMID: 2882444
  18. Spatial and temporal changes in signal transduction pathways during LTP.
    Neuron. 1994 Sep;13(3):737-45 PMID: 7917303
  19. Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience.
    Nature. 1995 May 25;375(6529):328-31 PMID: 7753198
  20. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus.
    Nature. 1991 Jan 10;349(6305):156-8 PMID: 1846031
  21. The inositol 1,4,5-trisphosphate pathway mediates cholinergic potentiation of rat hippocampal neuronal responses to NMDA.
    J Physiol. 1992 Feb;447:513-33 PMID: 1593457
  22. The Relative Contribution of NMDA Receptor Channels in the Expression of Long-term Potentiation in the Hippocampal CA1 Region.
    Eur J Neurosci. 1992;4(8):681-690 PMID: 12106312
  23. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3954-8 PMID: 7513428
  24. Molecular mechanisms for memory: second-messenger induced modifications of protein kinases in nerve cells.
    Annu Rev Neurosci. 1987;10:459-76 PMID: 3551762
  25. Regulation of NMDA receptors by tyrosine kinases and phosphatases.
    Nature. 1994 May 19;369(6477):233-5 PMID: 7514272
  26. LTP and memory: can we enhance the connection?
    Trends Neurosci. 1993 May;16(5):163-4 PMID: 7685935
  27. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.
    Science. 1992 Dec 18;258(5090):1903-10 PMID: 1361685
  28. Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions.
    Nature. 1995 Aug 31;376(6543):737-45 PMID: 7544443
  29. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.
    Science. 1995 Sep 22;269(5231):1737-40 PMID: 7569905
  30. A persistent postsynaptic modification mediates long-term potentiation in the hippocampus.
    Neuron. 1988 Dec;1(10):911-7 PMID: 2908443
  31. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  32. Expression of LTP by AMPA and/or NMDA receptors is determined by the extent of NMDA receptors activation during the tetanus.
    J Neurophysiol. 1995 Dec;74(6):2349-57 PMID: 8747197
  33. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A.
    Anal Biochem. 1981 Apr;112(2):195-203 PMID: 6266278
  34. Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5.
    J Neurosci. 1989 Sep;9(9):3040-57 PMID: 2552039
  35. Synaptic disinhibition during maintenance of long-term potentiation in the CA1 hippocampal subfield.
    Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3058-62 PMID: 8159706
  36. A role for protein kinases and phosphatases in the Ca(2+)-induced enhancement of hippocampal AMPA receptor-mediated synaptic responses.
    Neuron. 1994 Sep;13(3):635-43 PMID: 7917294
  37. A critical period for long-term potentiation at thalamocortical synapses.
    Nature. 1995 May 25;375(6529):325-8 PMID: 7753197
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.19.10457
Published
1996-09-17
Pages
10457-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38406
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.19.10457 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: product@genelibs.com

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