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Multiple Mechanisms for the Potentiation of AMPA Receptor-Mediated Transmission by α-Ca2+/Calmodulin-Dependent Protein Kinase II
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Some forms of activity-dependent synaptic potentiation require the activation of postsynaptic Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Activation of CaMKII has been shown to phosphorylate the glutamate receptor 1 subunit of the AMPA receptor (AMPAR), thereby affecting some of the properties of the receptor. Here, a recombinant, constitutively active form of alphaCaMKII tagged with the fluorescent marker green fluorescent protein (GFP) [alphaCaMKII(1-290)-enhanced GFP (EGFP)] was expressed in CA1 pyramidal neurons from hippocampal slices. The changes in glutamatergic transmission onto these cells were analyzed. AMPA but not NMDA receptor-mediated EPSCs were specifically potentiated in infected compared with nearby noninfected neurons. This potentiation was associated with a reduction in the proportion of synapses devoid of AMPARs. In addition, expression of alphaCaMKII(1-290)-EGFP increased the quantal size of AMPAR-mediated responses. This effect reflected, at least in part, an increased unitary conductance of the channels underlying the EPSCs. These results reveal that several key features of long-term potentiation of hippocampal glutamatergic synapses are reproduced by the sole activity of alphaCaMKII.
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“Expression of active CaMKII (121, 130–132, 209, 210, 212) or direct delivery into the cell via the recording electrode (199) has repeatedly revealed a roughly two- to threefold enhancement in the AMPAR EPSC but little change in the NMDAR EPSC (130–132).”
From Synaptic memory and CaMKII (2023) · cites this paper as [131]
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“The number of NMDARs does not change, since constitutively active CaMKII does not affect the NMDAR EPSC (130–132) and LTP is expressed primarily on the AMPAR (19).”
From Synaptic memory and CaMKII (2023) · cites this paper as [131]
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“The major form of LTP identified in the brain, NMDAR-dependent LTP, is the result of increased AMPAR density in the post-synaptic membrane and/or single channel conductance of the AMPAR (Huganir and Nicoll, 2013, Herring and Nicoll, 2016, Poncer et al., 2002, Benke et al., 1998).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Poncer et al., 2002
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“overexpression of constitutively active CaMKII has little effect on synaptic NMDAR responses (130–132).”
From Synaptic memory and CaMKII (2023) · cites this paper as [131]
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“since overexpression of PSD-95 on its own potentiates AMPAR EPSCs and occludes LTP (131, 297, 298) and the S73D mutant causes a similar potentiation.”
From Synaptic memory and CaMKII (2023) · cites this paper as [131]
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Metadata
- Authors
- Poncer, J. C., Esteban, J. A., & Malinow, R.
- Affiliations
- Inserm (FR)
- Cold Spring Harbor Laboratory (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-06-01
- Volume
- 22
- Issue
- 11
- Pages
- 4406-4411
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758819
- OpenAlex
- W1756593109
- Cited by
- 177
- References
- 46
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 1 · 2018: 7 · 2017: 3 · 2016: 3 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- G. Harold and Leila Y. Mathers Foundation
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- CaMKIIα, AMPA receptors, synaptic potentiation, long-term potentiation, CA1 pyramidal neurons, hippocampus, glutamatergic synapses, quantal size, single-channel conductance, activity-dependent synaptic plasticity, NMDA receptor
- MeSH terms
- Animals, Female, Hippocampus, Luminescent Proteins, Male, Synaptic Transmission, Neuronal Plasticity, Recombinant Fusion Proteins, Sindbis Virus, Gene Expression, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Pyramidal Cells, Receptors, AMPA, Patch-Clamp Techniques, Transgenes, Excitatory Postsynaptic Potentials, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques
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