Is Persistent Activity of Calcium/Calmodulin-Dependent Kinase Required for the Maintenance of LTP?
Abstract
Calcium/calmodulin-dependent protein kinase II (CaMKII) is concentrated in the postsynaptic density (PSD) and plays an important role in the induction of long-term potentiation (LTP). Because this kinase is persistently activated after the induction, its activity could also be important for LTP maintenance. Experimental tests of this hypothesis, however, have given conflicting results. In this paper we further explore the role of postsynaptic CaMKII in induction and maintenance of LTP. Postsynaptic application of a CaMKII inhibitor [autocamtide-3 derived peptide inhibitor (AC3-I), 2 mM] blocked LTP induction but had no detectable affect on N-methyl-D-aspartate (NMDA)-mediated synaptic transmission, indicating that the primary function of CaMKII in LTP is downstream from NMDA channel function. We next explored various methodological factors that could account for conflicting results on the effect of CaMKII inhibitors on LTP maintenance. In contrast to our previous work, we now carried out experiments at higher temperature (33 degrees C), used slices from adult animals, and induced LTP using a tetanic stimulation. However, we still found that LTP maintenance was not affected by postsynaptic application of AC3-I. Furthermore the inhibitor did not block LTP maintenance under conditions designed to enhance the Ca(2+)-dependent activity of protein phosphatases 1 and 2B (elevated Ca(2+), calmodulin, and an inhibitor of protein kinase A). We also tested the possibility that CaMKII in…
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Numerous studies using peptide inhibitors have confirmed the block of LTP.
“Numerous studies using peptide inhibitors have confirmed the block of LTP (200–203).”
From Synaptic memory and CaMKII (2023) · cites this paper as [201]
Pharmacological inhibition of CaMKII activity has generally been reported not to affect synaptic responses.
“In addition, pharmacological inhibition of CaMKII activity has generally been reported not to affect synaptic responses (198, 200–203, 357, 358).”
From Synaptic memory and CaMKII (2023) · cites this paper as [201]
Numerous previous studies have failed to reverse established LTP.
“However, numerous previous studies have failed to reverse established LTP (Refs. 198, 200–203, but see Ref. 357).”
From Synaptic memory and CaMKII (2023) · cites this paper as [201]
Concentrations of CaMKII inhibitors that block the induction of LTP failed to affect maintenance.
“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).”
From Synaptic memory and CaMKII (2023) · cites this paper as [201]
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- Authors
- Chen, H.-X., Otmakhov, N., Strack, S., Colbran, R. J., & Lisman, J. E.
- Affiliations
- Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454; and
- Brandeis University (US)
- Vanderbilt University (US)
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2001-04-01
- Volume
- 85
- Issue
- 4
- Pages
- 1368-1376
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2316453747
- Cited by
- 126
- References
- 70
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 7
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- 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, long-term potentiation, LTP maintenance, postsynaptic density, CaMKII inhibitor, NMDA receptor, calcineurin, protein phosphatase 1, calmodulin, autophosphorylation, tetanic stimulation, temperature effects, synaptic plasticity
- MeSH terms
- Animals, Electric Conductivity, Electrophysiology, Enzyme Inhibitors, Male, Peptides, Synapses, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Rats, Long-Evans, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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