Inhibition of Postsynaptic PKC or CaMKII Blocks Induction But Not Expression of LTP
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Long-term potentiation (LTP) of synaptic transmission is a widely studied cellular example of synaptic plasticity. However, the identity, localization, and interplay among the biochemical signals underlying LTP remain unclear. Intracellular microelectrodes have been used to record synaptic potentials and deliver protein kinase inhibitors to postsynaptic CA1 pyramidal cells. Induction of LTP is blocked by intracellular delivery of H-7, a general protein kinase inhibitor, or PKC(19-31), a selective protein kinase C (PKC) inhibitor, or CaMKII(273-302), a selective inhibitor of the multifunctional Ca2+-calmodulin-dependent protein kinase (CaMKII). After its establishment, LTP appears unresponsive to postsynaptic H-7, although it remains sensitive to externally applied H-7. Thus both postsynaptic PKC and CaMKII are required for the induction of LTP and a presynaptic protein kinase appears to be necessary for the expression of LTP.
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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 [198]
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 [198]
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 [198]
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 [198]
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 [198]
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- Authors
- Malinow, R., Schulman, H., & Tsien, R. W.
- Affiliations
- Stanford Medicine (US)
- Venue
- Science
- Published
- 1989-08-25
- Volume
- 245
- Issue
- 4920
- Pages
- 862-866
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2010920096
- Cited by
- 1,325
- References
- 2
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 14 · 2023: 11 · 2022: 15 · 2021: 13 · 2020: 17 · 2019: 20 · 2018: 24 · 2017: 15 · 2016: 21 · 2015: 27 · 2014: 27 · 2013: 22 · 2012: 34
- FWCI
- 27.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM 30179)
- National Institute of Neurological Disorders and Stroke (NS 24067)
- 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, CaMKII, LTP induction, synaptic plasticity, H-7, CA1 pyramidal neurons, hippocampus
- MeSH terms
- Animals, Isoquinolines, Synaptic Transmission, Piperazines, Protein Kinase C, Protein Kinases, Synapses, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, Neurotransmitter, Receptors, AMPA, Kainic Acid Receptors, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Protein Kinase Inhibitors, Rats, In Vitro Techniques
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