Calcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism
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Ca(2+)-sensitive kinases are thought to play a role in long-term potentiation (LTP). To test the involvement of Ca2+/calmodulin-dependent kinase II (CaM-K II), truncated, constitutively active form of this kinase was directly injected into CA1 hippocampal pyramidal cells. Inclusion of CaM-K II in the recording pipette resulted in a gradual increase in the size of excitatory postsynaptic currents (EPSCs). No change in evoked responses occurred when the pipette contained heat-inactivated kinase. The effects of CaM-K II mimicked several features of LTP in that it caused a decreased incidence of synaptic failures, an increase in the size of spontaneous EPSCs, and an increase in the amplitude of responses to iontophoretically applied alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. To determine whether the CaM-K II-induced enhancement and LTP share a common mechanism, occlusion experiments were carried out. The enhancing action of CaM-K II was greatly diminished by prior induction of LTP. In addition, following the increase in synaptic strength by CaM-K II, tetanic stimulation failed to evoke LTP. These findings indicate that CaM-K II alone is sufficient to augment synaptic strength and that this enhancement shares the same underlying mechanism as the enhancement observed with LTP.
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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 Lledo et al., 1995
CaMKII occludes LTP.
“This is indeed the case (199, 209).”
From Synaptic memory and CaMKII (2023) · cites this paper as [199]
In the occlusion experiment, the naive control pathway showed a robust enhancement, whereas the response on the pathway expressing LTP was greatly diminished.
“The naive control pathway showed a robust enhancement, whereas the response on the pathway expressing LTP was greatly diminished.”
From Synaptic memory and CaMKII (2023) · cites this paper as [199]
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- Authors
- Lledo, P. M., Hjelmstad, G. O., Mukherji, S., Soderling, T. R., Malenka, R. C., & Nicoll, R. A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-11-21
- Volume
- 92
- Issue
- 24
- Pages
- 11175-11179
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC40594
- OpenAlex
- W2036869107
- Cited by
- 456
- References
- 1
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 13 · 2022: 14 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 8 · 2015: 14 · 2014: 10 · 2013: 19 · 2012: 22
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS027037, NS 27037)
- 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, synaptic transmission, excitatory postsynaptic currents, CA1 pyramidal neurons, constitutively active kinase, synaptic plasticity, synaptic failure, tetanic stimulation
- MeSH terms
- Animals, Calcium, Enzyme Activation, Guinea Pigs, Hippocampus, Microinjections, Synaptic Transmission, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, AMPA, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques
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