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Cited by 248Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsTreatment of Major Depression

Role of the CaMKII/NMDA Receptor Complex in the Maintenance of Synaptic Strength

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Sanhueza, M., Fernandez-Villalobos, G., Stein, I. S., Kasumova, G., Zhang, P., Bayer, K. U., Otmakhov, N., Hell, J. W. +1 more·2011·Journal of Neuroscience
DOI 10.1523/jneurosci.1250-11.2011PMC PMC3138556
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Abstract

During long-term potentiation (LTP), synapses undergo stable changes in synaptic strength. The molecular memory processes that maintain strength have not been identified. One hypothesis is that the complex formed by the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the NMDA-type glutamate receptor (NMDAR) is a molecular memory at the synapse. To establish a molecule as a molecular memory, it must be shown that interfering with the molecule produces a persistent reversal of LTP. We used the CN class of peptides that inhibit CaMKII binding to the NR2B subunit in vitro to test this prediction in rat hippocampal slices. We found that CN peptides can reverse saturated LTP, allowing additional LTP to be induced. The peptide also produced a persistent reduction in basal transmission. We then tested whether CN compounds actually affect CaMKII binding in living cells. Application of CN peptide to slice cultures reduced the amount of CaMKII concentrated in spines, consistent with delocalization of the kinase from a binding partner in the spine. To more specifically assay the binding of CaMKII to the NMDAR, we used coimmunoprecipitation methods. We found that CN peptide decreased synaptic strength only at concentrations necessary to disrupt the CaMKII/NMDAR complex, but not at lower concentrations sufficient to inhibit CaMKII activity. Importantly, both the reduction of the complex and the reduction of synaptic strength persisted after removal of the inhibitor. These results support the hypothesis that the CaMKII/NMDAR complex has switch-like properties that are important in the maintenance of synaptic strength.

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  • CaMKII contributes to baseline synaptic transmission, as shown by peptide inhibitors, RNAi, and CRISPR.

    “The first evidence that CaMKII contributes to synaptic transmission came from expression of peptide inhibitors (150, 154).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [154]

  • The higher concentrations of inhibitor that do reverse LTP could result from the displacement of GluN2B bound to CaMKII.

    “The higher concentrations of inhibitor that do reverse LTP (154, 361) could result from the displacement of GluN2B bound to CaMKII.”

    From Synaptic memory and CaMKII (2023) · cites this paper as [154]

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Authors
Sanhueza, M., Fernandez-Villalobos, G., Stein, I. S., Kasumova, G., Zhang, P., Bayer, K. U., Otmakhov, N., Hell, J. W., & Lisman, J.
Affiliations
  • University of Chile (CL)
  • University of California, Davis (US)
  • Brandeis University (US)
  • University of Colorado Anschutz (US)
  • University of Massachusetts Chan Medical School (US)
ORCID
Venue
Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2011-06-22
Volume
31
Issue
25
Pages
9170-9178
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.1250-11.2011
PMC
PMC3138556
OpenAlex
W2007756386
Cited by
248
References
61
Citations by year
2026: 5 · 2025: 7 · 2024: 14 · 2023: 16 · 2022: 13 · 2021: 19 · 2020: 10 · 2019: 16 · 2018: 15 · 2017: 27 · 2016: 11 · 2015: 16 · 2014: 29 · 2013: 22 · 2012: 21
FWCI
10.60
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS027337, NS046450, R01NS046450, R01NS052644, T32NS007292, NS027337)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
CaMKII, NMDA receptor, synaptic plasticity, long-term potentiation, molecular memory, NR2B subunit, hippocampus, synaptic transmission, switch-like behavior
MeSH terms
Action Potentials, Animals, Cells, Cultured, Hippocampus, Male, Synaptic Transmission, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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