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CaMKII "Autonomy" Is Required for Initiating But Not for Maintaining Neuronal Long-Term Information Storage
Open accessAbstract
Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) "autonomy" (T286-autophosphorylation-induced Ca(2+)-independent activity) is required for long-term potentiation (LTP) and for learning and memory, as demonstrated by CaMKII T286A mutant mice. The >20-year-old hypothesis that CaMKII stimulation is required for LTP induction, while CaMKII autonomy is required for LTP maintenance was recently supported using the cell-penetrating fusion-peptide inhibitor antCN27. However, we demonstrate here that ant/penetratin fusion to CN27 compromised CaMKII-selectivity, by enhancing a previously unnoticed direct binding of CaM to ant/penetratin. In contrast to antCN27, the improved cell-penetrating inhibitor tatCN21 (5 mum) showed neither CaM binding nor inhibition of basal synaptic transmission. In vitro, tatCN21 inhibited stimulated and autonomous CaMKII activity with equal potency. In rat hippocampal slices, tatCN21 inhibited LTP induction, but not LTP maintenance. Correspondingly, tatCN21 also inhibited learning, but not memory storage or retrieval in a mouse in vivo model. Thus, CaMKII autonomy provides a short-term molecular memory that is important in the signal computation leading to memory formation, but is not required as long-term memory store.
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“Numerous studies using peptide inhibitors have confirmed the block of LTP (200–203).”
From Synaptic memory and CaMKII (2023) · cites this paper as [202]
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“In addition, pharmacological inhibition of CaMKII activity has generally been reported not to affect synaptic responses (198, 200–203, 357, 358).”
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“However, numerous previous studies have failed to reverse established LTP (Refs. 198, 200–203, but see Ref. 357).”
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“Third, as discussed in sect. 8, concentrations of CaMKII inhibitors that block the induction of LTP failed to affect maintenance (Refs. 198, 200–203, but see Ref. 357).”
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Metadata
- Authors
- Buard, I., Coultrap, S. J., Freund, R. K., Lee, Y.-S., Dell'Acqua, M. L., Silva, A. J., & Bayer, K. U.
- Affiliations
- University of Colorado Anschutz (US)
- University of California, Los Angeles (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-06-16
- Volume
- 30
- Issue
- 24
- Pages
- 8214-8220
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2891520
- OpenAlex
- W2028360365
- Cited by
- 160
- References
- 61
- Citations by year
- 2025: 10 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 15 · 2013: 18 · 2012: 17
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- University of Colorado Denver
- National Institute on Aging (R37AG013622)
- National Cancer Institute (P30CA046934)
- National Institute of Neurological Disorders and Stroke (P30NS048154, R01NS040701, R01NS052644)
- 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
- long-term potentiation, LTP maintenance, learning and memory, calmodulin binding, hippocampus, synaptic transmission
- MeSH terms
- Benzenesulfonamides, Animals, Behavior, Animal, Benzylamines, Carrier Proteins, Conditioning, Classical, Dose-Response Relationship, Drug, Electric Stimulation, Hippocampus, Male, Memory, Neural Inhibition, Neurons, Peptide Fragments, Phosphorylation, Recombinant Fusion Proteins, Sulfonamides, Viral Fusion Proteins, Rats, Sprague-Dawley, Long-Term Potentiation, Patch-Clamp Techniques, Protein Kinase Inhibitors, Mice, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cell-Penetrating Peptides, In Vitro Techniques
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