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Control of Synaptic Strength by Glial TNFα
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.
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“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).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Beattie et al. 2002
In the citing paper
“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).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Beattie et al. 2002
In the citing paper
“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).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Beattie et al. 2002
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Metadata
- 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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