Cited by 258Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsProtein Kinase Regulation and GTPase Signaling

Persistent accumulation of calcium/calmodulin-dependent protein kinase II in dendritic spines after induction of NMDA receptor-dependent chemical long-term potentiation

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Otmakhov, Nikolai, Tao-Cheng, Jung-Hwa, Carpenter, Stephen, Asrican, Brent, Dosemeci, Ayse, Reese, Thomas S., Lisman, John·2004·The Journal of Neuroscience

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate for a synaptic memory molecule because it is persistently activated after long-term potentiation (LTP) induction and because mutations that block this persistent activity prevent LTP and learning. Previous work showed that synaptic stimulation causes a rapidly reversible translocation of CaMKII to the synaptic region. We have now measured green fluorescent protein (GFP)-CaMKIIα translocation into synaptic spines during NMDA receptor-dependent chemical LTP (cLTP) and find that under these conditions, translocation is persistent. Using red fluorescent protein as a cell morphology marker, we found that there are two components of the persistent accumulation. cLTP produces a persistent increase in spine volume, and some of the increase in GFP-CaMKIIα is secondary to this volume change. In addition, cLTP results in a dramatic increase in the bound fraction of GFP-CaMKIIα in spines. To further study the bound pool, immunogold electron microscopy was used to measure CaMKIIα in the postsynaptic density (PSD), an important regulator of synaptic function. cLTP produced a persistent increase in the PSD-associated pool of CaMKIIα. These results are consistent with the hypothesis that CaMKIIα accumulation at synapses is a memory trace of past synaptic activity.

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Crossref · 10.1523/jneurosci.2350-04.2004

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  • Calcium ions play a crucial role in initiating downstream signaling during long-term potentiation (LTP) and depression (LTD) and influx of calcium is both necessary and sufficient for structural synaptic plasticity.

    “Calcium ions play a crucial role in initiating downstream signaling during long-term potentiation (LTP) and depression (LTD) and influx of calcium is both necessary and sufficient for structural synaptic plasticity (Pettit et al., 1994; Lledo et al., 1995; Otmakhov et al., 2004).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Otmakhov et al., 2004

    The Introduction (page unavailable) says Ca²⁺ entry through NMDA channels initiates LTP and activates CaMKII, supporting the LTP signaling portion. The paper also reports spine enlargement after chemical LTP, but it does not establish that calcium influx is both necessary and sufficient for structural synaptic plasticity or address calcium signaling during LTD. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • Chemical LTP induction results in persistent accumulation of CaMKIIα at the postsynaptic density in hippocampal synapses.

    “A–C: chemical long-term potentiation (chemLTP) induction results in persistent accumulation of CaMKIIα at the PSD.”

    From Synaptic memory and CaMKII (2023) · cites this paper as [217]

  • The persistent accumulation of CaMKII at the PSD following an LTP-inducing stimulus is shown in FIGURE 6, A-C.

    “The persistent accumulation of CaMKII at the PSD following an LTP-inducing stimulus is shown in FIGURE 6, A–C (217).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [217]

  • LTP-inducing stimuli result in the persistent accumulation of CaMKII in the PSD.

    “In addition, LTP-inducing stimuli result in the persistent accumulation of CaMKII in the PSD (FIGURE 6, A–C) (217).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [217]

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Authors
Otmakhov, N., Tao-Cheng, J.-H., Carpenter, S., Asrican, B., Dosemeci, A., Reese, T. S., & Lisman, J.
Affiliations
  • Brandeis University (US)
  • National Institute of Neurological Disorders and Stroke (US)
Venue
The Journal of Neuroscience
Published
2004-10-20
Volume
24
Issue
42
Pages
9324-9331
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2071910925
Cited by
258
References
53
Citations by year
2026: 2 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 8 · 2018: 17 · 2017: 10 · 2016: 7 · 2015: 13 · 2014: 23 · 2013: 11 · 2012: 18
FWCI
5.05
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion)
Funders
  • National Institutes of Health (R01 NS)
  • National Institute of Neurological Disorders and Stroke (R01NS027337, R01 NS27337)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
CaMKII, calcium/calmodulin-dependent protein kinase II, dendritic spines, NMDA receptor, postsynaptic density, synaptic memory, long-term potentiation, learning
MeSH terms
Adenylyl Cyclases, Animals, Colforsin, Phosphodiesterase Inhibitors, Protein Binding, Recombinant Fusion Proteins, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Rolipram, Protein Transport, Dendritic Spines, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques

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