Miniature Neurotransmission Stabilizes Synaptic Function via Tonic Suppression of Local Dendritic Protein Synthesis
Open accessAbstract
Activity deprivation in neurons induces a slow compensatory scaling up of synaptic strength, reflecting a homeostatic mechanism for stabilizing neuronal activity. Prior studies have focused on the loss of action potential (AP) driven neurotransmission in synaptic homeostasis. Here, we show that the miniature synaptic transmission that persists during AP blockade profoundly shapes the time course and mechanism of homeostatic scaling. A brief blockade of NMDA receptor (NMDAR) mediated miniature synaptic events ("minis") rapidly scales up synaptic strength, over an order of magnitude faster than with AP blockade alone. The rapid scaling induced by NMDAR mini blockade is mediated by increased synaptic expression of surface GluR1 and the transient incorporation of Ca2+-permeable AMPA receptors at synapses; both of these changes are implemented locally within dendrites and require dendritic protein synthesis. These results indicate that NMDAR signaling during miniature synaptic transmission serves to stabilize synaptic function through active suppression of dendritic protein synthesis.
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When global block of firing with TTX is combined with local glutamate receptor block, there is a local enhancement of GluA1 accumulation at the blocked synapses.
“Interestingly, when global block of firing with TTX is combined with local glutamate receptor block, there is a local enhancement of GluA1 accumulation at the blocked synapses (Sutton et al. 2006).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Sutton et al. 2006
Enhanced AMPAR accumulation under conditions of both action potential and NMDAR block involves local synthesis and insertion of GluA1-containing/GluA2-lacking AMPAR into synapses, so that the synaptic composition of AMPAR is modified.
“Enhanced AMPAR accumulation under conditions of both action potential and NMDAR block involves local synthesis and insertion of GluA1-containing/GluA2-lacking AMPAR into synapses, so that the synaptic composition of AMPAR is modified (Ju et al. 2004;Sutton et al. 2006;Aoto et al. 2008).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Sutton et al. 2006
Scaling is a gradual and cumulative process evident after as little as 4-6 h of activity blockade.
“Inconsistent with the above model is the observation that scaling is a gradual and cumulative process evident after as little as 4-6 h of activity blockade (Sutton et al. 2006;Ibata et al. 2008), whereas TNFa-dependent scaling was only observed after prolonged activity block (48 h) (Stellwagen and Malenka 2006).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Sutton et al. 2006
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- Authors
- Sutton, M. A., Ito, H. T., Cressy, P., Kempf, C., Woo, J. C., & Schuman, E. M.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Schuman, Erin M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 125
- Issue
- 4
- Pages
- 785-799
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2031779883
- Cited by
- 633
- References
- 3
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 21 · 2023: 31 · 2022: 19 · 2021: 29 · 2020: 33 · 2019: 27 · 2018: 39 · 2017: 26 · 2016: 26 · 2015: 33 · 2014: 32 · 2013: 51 · 2012: 47
- FWCI
- 12.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2670 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- synaptic homeostasis, NMDA receptor signaling, GluR1, Ca2+-permeable AMPA receptors, dendritic protein synthesis, synaptic scaling, activity deprivation, action potential blockade, synaptic plasticity
- MeSH terms
- Action Potentials, Animals, Cells, Cultured, Cobalt, Dendrites, Hippocampus, Homeostasis, Nerve Tissue Proteins, Synaptic Transmission, Synapses, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Patch-Clamp Techniques, Excitatory Amino Acid Agonists, Excitatory Postsynaptic Potentials, Protein Subunits, Rats, In Vitro Techniques
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