Cited by 1,139Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionGenetics and Neurodevelopmental Disorders

The DOI matches its Crossref record; 109 of the 110 references it cites were found in a registry or an index; 62 of the 157 sources its claims cite were checked for support.

Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function

Open access
Turrigiano, G.·2012·Cold Spring Harbor Perspectives in Biology

Abstract

Neural circuits must maintain stable function in the face of many plastic challenges, including changes in synapse number and strength, during learning and development. Recent work has shown that these destabilizing influences are counterbalanced by homeostatic plasticity mechanisms that act to stabilize neuronal and circuit activity. One such mechanism is synaptic scaling, which allows neurons to detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. Additional homeostatic mechanisms may allow local changes in synaptic activation to generate local synaptic adaptations, and network-wide changes in activity to generate network-wide adjustments in the balance between excitation and inhibition. The signaling pathways underlying these various forms of homeostatic plasticity are currently under intense scrutiny, and although dozens of molecular pathways have now been implicated in homeostatic plasticity, a clear picture of how homeostatic feedback is structured at the molecular level has not yet emerged. On a functional level, neuronal networks likely use this complex set of regulatory mechanisms to achieve homeostasis over a wide range of temporal and spatial scales.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Homeostatic synaptic plasticity stabilizes neuronal firing through mechanisms such as synaptic scaling, which uses calcium-dependent sensors to bidirectionally regulate glutamate receptor accumulation at synapses. The review distinguishes global, cell-autonomous scaling from local/quasi-local and network-level mechanisms, and highlights that the molecular logic of homeostatic feedback remains incompletely understood.

Key findings

  • Synaptic scaling is a cell-autonomous, global form of homeostatic plasticity: perturbing activity bidirectionally scales quantal amplitude (mEPSC/mini amplitude) up or down, regulating both AMPA and NMDA currents proportionally, and requires the GluA2 subunit of AMPARs.
  • Scaling up and scaling down share some calcium/CaMKK/CaMKIV signaling but diverge in other molecular requirements; for example, scaling up depends completely on PSD-95, whereas scaling down can be supported by either PSD-95 or PSD-93.
  • Local or quasi-local homeostatic mechanisms also exist: combined TTX and glutamate receptor block locally enhances GluA1-containing/GluA2-lacking AMPAR insertion via retinoic acid/RARα, and presynaptic release probability can be regulated quasi-locally by dendritic depolarization.
  • Network-level and secreted-factor mechanisms contribute to excitation/inhibition balance: BDNF and glial TNFα are implicated, with TNFα suggested to be permissive/maintenance rather than instructive for scaling; in vivo visual deprivation can scale mEPSC amplitude and insert GluA2-containing AMPARs.

Methods

  • This is a review article, not a primary experimental study; it synthesizes findings from in vitro and in vivo work on homeostatic synaptic plasticity at the neuromuscular junction and central mammalian synapses.
  • The paper reviews signaling pathways, expression mechanisms, and functional roles of synaptic scaling, local/quasi-local plasticity, secreted factors, and synapse-type-specific rules.
  • No new experimental sample, dataset, or statistical analysis is reported.

Limitations

  • Stated: the signaling pathways underlying homeostatic plasticity are under intense scrutiny, but “a clear picture of how homeostatic feedback is structured at the molecular level has not yet emerged.”
  • Stated: whether mechanisms underlying synaptic scaling in vivo and in other brain regions are similar to or distinct from those in cultured cortical neurons remains an open question.
  • Stated: local homeostatic regulation remains controversial, and the physiological significance of some presynaptic changes, such as VGlut changes, remains to be determined. Evident: as a narrative review, it does not systematically quantify evidence or resolve conflicting findings across studies.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1101/cshperspect.a005736

Cites

109 of 109 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

62 of 157 cited sources checked · 34 supported · 2 flagged · accuracy not yet measured

Show all 76 claims

  • It may state two separate claims as one. 41
  • Probably not a substantial claim. 8
48 of 48
  • The paper relies on this without support.

    Neural circuits must maintain stable function in the face of plastic challenges including changes in synapse number and strength during learning and development.

    “Neural circuits must maintain stable function in the face of many plastic challenges, including changes in synapse number and strength, during learning and development.”
  • The paper relies on this without support.

    At the neuromuscular junction, as muscle fibers grow, motor neurons must remain capable of bringing them over threshold for contraction.

    “The stability problem at the neuromuscular junction (NMJ) is fairly simple: As muscle fibers grow, motor neurons must remain capable of bringing them over threshold for contraction.”
  • The paper relies on this without support.

    The forces that generate flexibility and those that generate stability are able to coexist without interfering with each other.

    “Somehow the forces that generate flexi-bility and those that generate stability are able to coexist without interfering with each other, and together enable the remarkable ability of organisms to generate behaviors that are both coherent and adaptable.”
3 of 3

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Each contradiction between two passages listed here was confirmed by an independent check.

  • Evers study has conflicting publication years

    Minor

    The text cites the Evers study as published in 2011, but the corresponding reference lists it as published in 2010.

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Metadata

Authors
Turrigiano, G.
Affiliations
Brandeis University (US)
Corresponding author
Turrigiano, G.
Venue
Cold Spring Harbor Perspectives in Biology
Published
2011-11-15
Volume
4
Issue
1
Pages
a005736-a005736
ISSN
1943-0264 (ISSN-L)
OpenAlex
W2115900486
Cited by
1,139
References
110
Citations by year
2026: 95 · 2025: 98 · 2024: 82 · 2023: 92 · 2022: 91 · 2021: 107 · 2020: 92 · 2019: 80 · 2018: 77 · 2017: 89 · 2016: 59 · 2015: 69 · 2014: 41 · 2013: 51 · 2012: 15
Type
posted content
Language
en
Open access
Locations
  • Cold Spring Harbor Perspectives in Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
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
homeostatic plasticity, synaptic scaling, glutamate receptor trafficking, excitation-inhibition balance, neuronal firing rate
MeSH terms
Animals, Homeostasis, Humans, Nerve Net, Neuromuscular Junction, Neuronal Plasticity, Neurons, Synapses

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