In Vivo Synaptic Scaling Is Mediated by GluA2-Lacking AMPA Receptors in the Embryonic Spinal Cord
Open accessAbstract
When spiking activity within a network is perturbed for hours to days, compensatory changes in synaptic strength are triggered that are thought to be important for the homeostatic maintenance of network or cellular spiking activity. In one form of this homeostatic plasticity, called synaptic scaling, all of a cell's AMPAergic miniature postsynaptic currents (mEPSCs) are increased or decreased by some scaling factor. Although synaptic scaling has been observed in a variety of systems, the mechanisms that underlie AMPAergic scaling have been controversial. Certain studies find that synaptic scaling is mediated by GluA2-lacking calcium receptors (CP-AMPARs), whereas others have found that scaling is mediated by GluA2-containing calcium-impermeable receptors (CI-AMPARs). Spontaneous network activity is observed in most developing circuits, and in the spinal cord this activity drives embryonic movements. Blocking spontaneous network activity in the chick embryo by infusing lidocaine in vivo triggers synaptic scaling in spinal motoneurons; here we show that AMPAergic scaling occurs through increases in mEPSC conductance that appear to be mediated by the insertion of GluA2-lacking AMPA receptors at the expense of GluA2-containing receptors. We have previously reported that in vivo blockade of GABAA transmission, at a developmental stage when GABA is excitatory, also triggered AMPAergic synaptic scaling. Here, we show that this form of AMPAergic scaling is also mediated by CP-AMPARs. These findings suggest that AMPAergic scaling triggered by blocking spiking activity or GABAA receptor transmission represents similar phenomena, supporting the idea that activity blockade triggers scaling by reducing GABAA transmission.
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The presence of these receptors changes the rules for the induction of plasticity and mediates in vivo synaptic scaling.
“Furthermore, the presence of these receptors changes the rules for the induction of plasticity (Mameli et al., 2011) and mediates in vivo synaptic scaling (Garcia-Bereguiain et al., 2013).”
From Oxytocin neurons mediate the effect of social isolation via the VTA circuits (2022) · cites this paper as Garcia-Bereguiain et al., 2013
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- Vitureira N Letellier M Goda Y 2012 Homeostatic synaptic plasticity: from single synapses to neural circuits Curr Opin Neurobiol 22 516 521 21983330 PMC3378479
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- Authors
- Garcia-Bereguiain, M. A., Gonzalez-Islas, C., Lindsly, C., Butler, E., Hill, A. W., & Wenner, P.
- Affiliations
- Emory University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-04-17
- Volume
- 33
- Issue
- 16
- Pages
- 6791-6799
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3661002
- OpenAlex
- W2004035019
- Cited by
- 26
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 3
- FWCI
- 2.13
- 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)
- Europe PMC (PubMed Central) (acceptedVersion)
- Journal of Neuroscience Nursing
- Funders
- Whitehall Foundation
- Craig H. Neilsen Foundation
- Fundación Rafael del Pino
- National Institute of Neurological Disorders and Stroke (R01NS065992)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- synaptic scaling, homeostatic plasticity, miniature postsynaptic currents, spinal motoneurons, embryonic spinal cord, spontaneous network activity, lidocaine, chick embryo, AMPA receptor subunit composition
- MeSH terms
- Anesthetics, Local, Animals, Biophysics, Chick Embryo, Electric Stimulation, Lidocaine, Motor Neurons, Pyridazines, Spinal Cord, Synapses, Tetrodotoxin, Receptors, AMPA, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, Excitatory Amino Acid Antagonists, GABA Antagonists, Excitatory Postsynaptic Potentials
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