An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation
Abstract
The phenomenon of long-term potentiation (LTP), a long lasting increase in the strength of synaptic transmission which is due to brief, repetitive activation of excitatory afferent fibres, is one of the most striking examples of synaptic plasticity in the mammalian brain. In the CA1 region of the hippocampus, the induction of LTP requires activation of NMDA (N-methyl-D-aspartate) receptors by synaptically released glutamate with concomitant postsynaptic membrane depolarization. This relieves the voltage-dependent magnesium block of the NMDA-receptor ion channel, allowing calcium to flow into the dendritic spine. Although calcium has been shown to be a necessary trigger for LTP (refs 11, 12), little is known about the immediate biochemical processes that are activated by calcium and are responsible for LTP. The most attractive candidates have been calcium/calmodulin-dependent protein kinase II (CaM-KII) (refs 13-16), protein kinase C (refs 17-19), and the calcium-dependent protease, calpain. Extracellular application of protein kinase inhibitors to the hippocampal slice preparation blocks the induction of LTP (refs 21-23) but it is unclear whether this is due to a pre- and/or postsynaptic action. We have found that intracellular injection into CA1 pyramidal cells of the protein kinase inhibitor H-7, or of the calmodulin antagonist calmidazolium, blocks LTP. Furthermore, LTP is blocked by the injection of synthetic peptides that are potent calmodulin antagonists and inhibit CaM…
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When the intracellular electrode contained a CaMKII inhibitory peptide, LTP was blocked in the individual cell but not the population.
“When the intracellular electrode contained a CaMKII inhibitory peptide, LTP was blocked in the individual cell but not the population.”
From Synaptic memory and CaMKII (2023) · cites this paper as [197]
Infusion of CaMKII peptide inhibitors in the postsynaptic cell blocked LTP.
“infusion of CaMKII peptide inhibitors in the postsynaptic cell blocked LTP (197, 198)”
From Synaptic memory and CaMKII (2023) · cites this paper as [197]
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References 39 · Cited by 1,025
- Authors
- Malenka, R. C., Kauer, J. A., Perkel, D. J., Mauk, M. D., Kelly, P. T., Nicoll, R. A., & Waxham, M. N.
- Affiliations
- University of California, San Francisco (US)
- The University of Texas Health Science Center at Houston (US)
- Venue
- Nature
- Published
- 1989-08
- Volume
- 340
- Issue
- 6234
- Pages
- 554-557
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2012974904
- Cited by
- 1,025
- References
- 39
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 15 · 2018: 15 · 2017: 6 · 2016: 22 · 2015: 23 · 2014: 17 · 2013: 15 · 2012: 23
- FWCI
- 20.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (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
- long-term potentiation, calmodulin, calcium/calmodulin-dependent protein kinase II, postsynaptic signaling, synaptic plasticity, NMDA receptor, CA1 pyramidal neurons, calmodulin antagonists, calmidazolium, H-7, protein kinase inhibitors
- MeSH terms
- Animals, Calmodulin, Isoquinolines, Synaptic Transmission, Piperazines, Protein Kinases, Synapses, Calcium-Calmodulin-Dependent Protein Kinases, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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