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Cited by 688Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingGenetics and Neurodevelopmental Disorders

Activity-Dependent Modulation of Synaptic AMPA Receptor Accumulation

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O’Brien, Richard J, Kamboj, Sunjeev, Ehlers, Michael D, Rosen, Kenneth R, Fischbach, Gerald D, Huganir, Richard L·1998·Neuron
DOI 10.1016/s0896-6273(00)80624-8
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Abstract

Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors.

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  • The majority of studies that have blocked activity with TTX or AMPAR antagonists have observed a coordinated increase in GluA1 and GluA2.

    “the majority of studies that have blocked activity with tetrodotoxin (TTX) or AMPAR antagonists have observed a coordinated increase in GluA1 and GluA2 (O'Brien et al. 1998;Wierenga et al. 2005;Cingolani et al. 2008;Sun and Wolf 2009;Anggono et al. 2011; but see Thiagarajan et al. 2005).”

    From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as O'Brien et al. 1998

  • Synaptic scaling has been shown in a variety of central neurons both in vitro and in vivo, including neocortical and hippocampal pyramidal neurons and spinal neurons.

    “Synaptic scaling has now been shown in a variety of central neurons both in vitro and in vivo, including neocortical and hippocampal pyramidal neurons and spinal neurons (O'Brien et al. 1998;Turrigiano et al. 1998;Desai et al. 2002;Stellwagen and Malenka 2006;Goel and Lee 2007;Kim and Tsien 2008;Knogler et al. 2010).”

    From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as O'Brien et al. 1998

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Authors
O’Brien, R. J., Kamboj, S., Ehlers, M. D., Rosen, K. R., Fischbach, G. D., & Huganir, R. L.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Harvard University (US)
Corresponding author
Huganir, Richard L
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
1998-11
Volume
21
Issue
5
Pages
1067-1078
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/s0896-6273(00)80624-8
OpenAlex
W2066781880
Cited by
688
References
0
Citations by year
2026: 10 · 2025: 28 · 2024: 20 · 2023: 11 · 2022: 20 · 2021: 23 · 2020: 27 · 2019: 29 · 2018: 25 · 2017: 23 · 2016: 21 · 2015: 27 · 2014: 17 · 2013: 35 · 2012: 23
FWCI
9.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS036715, K08NS001652)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
AMPA receptors, synaptic plasticity, synaptic remodeling, excitatory synaptic transmission, miniature EPSCs, GluR1 subunit, receptor turnover, spinal cord neurons, activity-dependent modulation
MeSH terms
Animals, Cells, Cultured, Half-Life, Kinetics, Synaptic Transmission, Picrotoxin, Spinal Cord, Strychnine, Synapses, 2-Amino-5-phosphonovalerate, Receptors, AMPA, 6-Cyano-7-nitroquinoxaline-2,3-dione, Excitatory Postsynaptic Potentials, Rats

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