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Synaptic Scaling Requires the GluR2 Subunit of the AMPA Receptor
Open accessAbstract
Two functionally distinct forms of synaptic plasticity, Hebbian long-term potentiation (LTP) and homeostatic synaptic scaling, are thought to cooperate to promote information storage and circuit refinement. Both arise through changes in the synaptic accumulation of AMPA receptors (AMPARs), but whether they use similar or distinct receptor-trafficking pathways is unknown. Here, we show that TTX-induced synaptic scaling in cultured visual cortical neurons leads to the insertion of GluR2-containing AMPARs at synapses. Similarly, visual deprivation with monocular TTX injections results in synaptic accumulation of GluR2-containing AMPARs. Unlike chemical LTP, synaptic scaling is blocked by a GluR2 C-tail peptide but not by a GluR1 C-tail peptide. Knockdown of endogenous GluR2 with an short hairpin RNA (shRNA) also blocks synaptic scaling but not chemical LTP. Scaling can be rescued with expression of exogenous GluR2 resistant to the shRNA, but a chimeric GluR2 subunit with the C-terminal domain swapped with the GluR1 C-terminal domain (GluR2/CT1) does not rescue synaptic scaling, indicating that regulatory sequences on the GluR2 C-tail are required for the accumulation of synaptic AMPARs during scaling. Together, our results suggest that synaptic scaling and LTP use different trafficking pathways, making these two forms of plasticity both functionally and molecularly distinct.
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“One such mechanism is synaptic scaling, which allows neurons to detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites.”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Gainey et al. 2009
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In the citing paper
“by measuring minis arising from many synapses onto the same neuron, it was observed that modulating network activity induced uniform increases or decreases in the entire mini amplitude distribution, in effect scaling postsynaptic strength up or down (Turrigiano et al. 1998;Desai et al. 2002;Gainey et al. 2009).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Gainey et al. 2009
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“This global enhancement of AMPAR abundance in response to activity blockade requires sequences on the carboxyl terminus of the GluA2 subunit of the AMPAR (Gainey et al. 2009)”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Gainey et al. 2009
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“It is worth noting, however, that postsynaptic knockdown of GluA2 is able to completely block synaptic scaling (Gainey et al. 2009), suggesting that if there is a presynaptic change in transmitter packaging it is not sufficient to enhance mini amplitude on its own.”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Gainey et al. 2009
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“Visual deprivation induced by optic nerve block scale ups mEPSC amplitude in vivo as in vitro, and results in insertion of GluA2-containing AMPAR (Desai et al. 2002;Maffei and Turrigiano 2008;Gainey et al. 2009).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Gainey et al. 2009
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“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 Gainey et al., 2009
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“Scaling-up can be rescued by expression of shRNA-resistant WT GluA2, but not by a GluA2 chimera with the C-tail swapped for GluA1, suggesting that elements of the GluA2 C-terminus are required for scaling-up (Gainey et al., 2009).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Gainey et al., 2009
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Citations
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Metadata
- Authors
- Gainey, M. A., Hurvitz-Wolff, J. R., Lambo, M. E., & Turrigiano, G. G.
- Affiliations
- Brandeis University (US)
- Corresponding author
- Turrigiano, Gina G.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-05-20
- Volume
- 29
- Issue
- 20
- Pages
- 6479-6489
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2714274
- OpenAlex
- W2011046807
- Cited by
- 234
- References
- 52
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 10 · 2018: 19 · 2017: 11 · 2016: 14 · 2015: 7 · 2014: 12 · 2013: 30 · 2012: 22
- FWCI
- 8.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS 36853)
- National Institute of Neurological Disorders and Stroke (NS 36853, R56NS036853, F31NS063532, R01NS036853)
- 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 › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- synaptic scaling, GluR2 subunit, AMPA receptors, long-term potentiation, homeostatic plasticity, receptor trafficking, GluR1, visual cortex, visual deprivation, tetrodotoxin, synaptic plasticity
- MeSH terms
- Disks Large Homolog 4 Protein, Adamantane, Analysis of Variance, Animals, Animals, Newborn, Biophysics, Cells, Cultured, Electric Stimulation, Membrane Proteins, Neurons, Synapses, Tetrodotoxin, Transfection, Visual Cortex, Long-Term Potentiation, Receptors, AMPA, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Excitatory Postsynaptic Potentials, Rats, Long-Evans, Sodium Channel Blockers, RNA Interference, RNA, Small Interfering, Intracellular Signaling Peptides and Proteins, Rats, In Vitro Techniques
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