Synaptic homeostasis requires the membrane-proximal carboxy tail of GluA2
Open accessAbstract
Bidirectional scaling of synaptic transmission, expressed as a compensatory change in quantal size following chronic activity perturbation, is a critical effector mechanism underlying homeostatic plasticity in the brain. An emerging model posits that the GluA2 AMPA receptor (AMPAR) subunit may be important for the bidirectional scaling of excitatory transmission; however, whether this subunit plays an obligatory role in synaptic scaling, and the identity of the precise domain(s) involved, remain controversial. We set out to determine the specific AMPAR subunit required for scaling up in CA1 hippocampal pyramidal neurons, and found that the GluA2 subunit is both necessary and sufficient. In addition, our results point to a critical role for a single amino acid within the membrane-proximal region of the GluA2 cytoplasmic tail, and suggest a distinct model for the regulation of AMPAR trafficking in synaptic homeostasis.
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Scaling-up can be blocked by expression of the soluble cytosolic C-terminal tail of GluA2 or by shRNA-mediated knock-down of GluA2.
“Scaling-up can be blocked by the expression of the soluble cytosolic C-terminal tail of GluA2 or by shRNA-mediated knock-down of GluA2 (Gainey et al., 2009, Ancona Esselmann et al., 2017).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Ancona Esselmann et al., 2017
Forms of LTP, LTD and homeostatic scaling have been shown to be intact in knock-out mice of different AMPAR subunits as well as in molecular replacement experiments.
“Forms of LTP, LTD and homeostatic scaling have been shown to be intact in knock-out mice of different AMPAR subunits as well as in using molecular replacement experiments (Huganir and Nicoll, 2013, Granger et al., 2013, Ancona Esselmann et al., 2017).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Ancona Esselmann et al., 2017
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References 35 · Cited by 35
- Authors
- Ancona Esselmann, S. G., Díaz-Alonso, J., Levy, J. M., Bemben, M. A., & Nicoll, R. A.
- Affiliations
- Neuroscience Graduate Program, University of California, San Francisco, CA 94158;
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-11-27
- Volume
- 114
- Issue
- 50
- Pages
- 13266-13271
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5740628
- OpenAlex
- W2769454340
- Cited by
- 35
- References
- 35
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 3 · 2018: 6
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (R01MH070957)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- synaptic homeostasis, GluA2, AMPA receptors, synaptic scaling, quantal size, homeostatic plasticity, CA1 pyramidal neurons, hippocampus, excitatory synaptic transmission
- MeSH terms
- Protein Domains, Animals, Homeostasis, Synapses, Pyramidal Cells, Receptors, AMPA, Protein Transport, Mice, Synaptic Potentials, CA1 Region, Hippocampal
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