Cited by 1,344Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsGenetics and Neurodevelopmental Disorders

Control of Synaptic Strength by Glial TNFα

Beattie, Eric C., Stellwagen, David, Morishita, Wade, Bresnahan, Jacqueline C., Ha, Byeong Keun, Von Zastrow, Mark, Beattie, Michael S., Malenka, Robert C.·2002·Science

Abstract

Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFalpha has the opposite effects. Thus, the continual presence of TNFalpha is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury.

Integrity signals

Registry

Crossref · 10.1126/science.1067859

Cites

22 of 22 references verified0 citation errors · 0 not checkable

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  • Acute application of TNFa or conditioned media from activity-blocked cultures increases mEPSC amplitude.

    “This model is based on the observations that TNFa levels are elevated by prolonged (48 h) activity blockade, acute application of TNFa (or conditioned media from activity-blocked cultures) increases mEPSC amplitude, and scaling up in response to prolonged activity blockade is prevented by blocking TNFa signaling (Beattie et al. 2002;Stellwagen et al. 2005;Stellwagen and Malenka 2006).”
  • TNFa levels are elevated by prolonged (48 h) activity blockade.

    “This model is based on the observations that TNFa levels are elevated by prolonged (48 h) activity blockade, acute application of TNFa (or conditioned media from activity-blocked cultures) increases mEPSC amplitude, and scaling up in response to prolonged activity blockade is prevented by blocking TNFa signaling (Beattie et al. 2002;Stellwagen et al. 2005;Stellwagen and Malenka 2006).”
  • Scaling up in response to prolonged activity blockade is prevented by blocking TNFa signaling.

    “This model is based on the observations that TNFa levels are elevated by prolonged (48 h) activity blockade, acute application of TNFa (or conditioned media from activity-blocked cultures) increases mEPSC amplitude, and scaling up in response to prolonged activity blockade is prevented by blocking TNFa signaling (Beattie et al. 2002;Stellwagen et al. 2005;Stellwagen and Malenka 2006).”

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Research works printed but not linked: 2

  1. Supplementary material is available on Science Online at www.sciencemag.org/cgi/content/full/295/5563/2282/DC1
  2. M. Noble M. Mayer-Proschel in Culturing Nerve Cells G. Banker K. Goslin Eds. (MIT Press Cambridge MA ed. 2 1998) pp. 526–529.

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Authors
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C.
Affiliations
  • Stanford Medicine (US)
  • The Ohio State University Wexner Medical Center (US)
  • Departments of Psychiatry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
Corresponding author
  • Beattie, Michael S.
  • Malenka, Robert C.
Venue
Science
Published
2002-03-22
Volume
295
Issue
5563
Pages
2282-2285
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1548862642
Cited by
1,344
References
22
Citations by year
2026: 36 · 2025: 33 · 2024: 47 · 2023: 58 · 2022: 57 · 2021: 82 · 2020: 65 · 2019: 56 · 2018: 59 · 2017: 67 · 2016: 58 · 2015: 61 · 2014: 64 · 2013: 73 · 2012: 73
FWCI
14.84
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (MH 063394)
  • National Institute on Drug Abuse (DA 00439)
  • National Institute of Neurological Disorders and Stroke (NS38079, R01NS031193, R01NS038079, NS 31193)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
synaptic efficacy, AMPA receptor trafficking, synaptic plasticity, excitatory synapses, nerve injury
MeSH terms
Animals, Astrocytes, Cells, Cultured, Gene Expression Regulation, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Neurons, Synapses, Tumor Necrosis Factor-alpha, Antigens, CD, Culture Media, Conditioned, Rats, Sprague-Dawley, Receptors, AMPA, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Rats

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