CaMKII binding to GluN2B is critical during memory consolidation

Amy R. Halt, Robert F. Dallapiazza, Yu Zhou, Ivar S. Stein, Hai Qian, Scott Juntti, Sonja Wojcik, Nils Brose, Alcino J. Silva, Johannes W Hell

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

Memory is essential for our normal daily lives and our sense of self. Ca 2+ influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca 2+ and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca 2+ influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca 2+-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24 h, but not 1-2 h, after training potentially due to impaired consolidation.

Original languageEnglish (US)
Pages (from-to)1203-1216
Number of pages14
JournalEMBO Journal
Volume31
Issue number5
DOIs
StatePublished - Mar 7 2012

Keywords

  • AMPA receptor
  • CaMKII
  • LTP
  • memory
  • NMDA receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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    Halt, A. R., Dallapiazza, R. F., Zhou, Y., Stein, I. S., Qian, H., Juntti, S., Wojcik, S., Brose, N., Silva, A. J., & Hell, J. W. (2012). CaMKII binding to GluN2B is critical during memory consolidation. EMBO Journal, 31(5), 1203-1216. https://doi.org/10.1038/emboj.2011.482