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Cited by 280Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Microglia Actively Regulate the Number of Functional Synapses

Open access
Ji, Kyungmin, Akgul, Gulcan, Wollmuth, Lonnie P., Tsirka, Stella E.·2013·PLoS ONE
DOI 10.1371/journal.pone.0056293PMC PMC3564799
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Abstract

Microglia are the immunocompetent cells of the central nervous system. In the physiological setting, their highly motile processes continually survey the local brain parenchyma and transiently contact synaptic elements. Although recent work has shown that the interaction of microglia with synapses contributes to synaptic remodeling during development, the role of microglia in synaptic physiology is just starting to get explored. To assess this question, we employed an electrophysiological approach using two methods to manipulate microglia in culture: organotypic hippocampal brain slices in which microglia were depleted using clodronate liposomes, and cultured hippocampal neurons to which microglia were added. We show here that the frequency of excitatory postsynaptic current increases in microglia-depleted brain slices, consistent with a higher synaptic density, and that this enhancement ensures from the loss of microglia since it is reversed when the microglia are replenished. Conversely, the addition of microglia to neuronal cultures decreases synaptic activity and reduces the density of synapses, spine numbers, surface expression of AMPA receptor (GluA1), and levels of synaptic adhesion molecules. Taken together, our findings demonstrate that non-activated microglia acutely modulate synaptic activity by regulating the number of functional synapses in the central nervous system.

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Crossref · 10.1371/journal.pone.0056293

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  • Microglia actively regulate neuronal synapses in a healthy physiological setting, and processes mediating this function can become aberrant in a neurodegenerative disease context, as in early stages of AD.

    “Microglia actively regulate neuronal synapses in a healthy physiological setting, and processes mediating this function can become aberrant in a neurodegenerative disease context, as in early stages of AD [15, 143, 179].”

    From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [179]

    The Results and Discussion show that resting microglia regulate synaptic numbers and activity, supporting the claim about a physiological setting. The paper does not establish that these processes become aberrant in neurodegenerative disease or in early Alzheimer’s disease. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 21

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Authors
Ji, K., Akgul, G., Wollmuth, L. P., & Tsirka, S. E.
Affiliations
Stony Brook University (US)
Corresponding author
  • Wollmuth, Lonnie P.
  • Tsirka, Stella E.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-02-05
Volume
8
Issue
2
Pages
e56293
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0056293
PMC
PMC3564799
OpenAlex
W2164222787
Cited by
280
References
7
Citations by year
2026: 6 · 2025: 12 · 2024: 17 · 2023: 27 · 2022: 23 · 2021: 35 · 2020: 25 · 2019: 30 · 2018: 20 · 2017: 21 · 2016: 21 · 2015: 18 · 2014: 16 · 2013: 9
FWCI
11.97
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institute of Mental Health (MH066892, R01MH066892)
  • National Eye Institute (R01EY016979)
  • National Institute of Neurological Disorders and Stroke (R01NS042168, NS42168)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
microglia, synaptic regulation, synaptic density, excitatory postsynaptic currents, microglia depletion, clodronate liposomes, organotypic hippocampal slices, hippocampal neurons, dendritic spines, AMPA receptors, GluR1, synaptic adhesion molecules, synaptic remodeling, microglia-neuron interaction
MeSH terms
Animals, Central Nervous System, Hippocampus, Immunohistochemistry, Mice, Inbred C57BL, Synapses, Blotting, Western, Microglia, Receptors, AMPA, Mice

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