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Cited by 178Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Microglia as hackers of the matrix: sculpting synapses and the extracellular space

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Crapser, Joshua D., Arreola, Miguel A., Tsourmas, Kate I., Green, Kim N.·2021·Cellular & Molecular Immunology
DOI 10.1038/s41423-021-00751-3PMC PMC8546068
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Abstract

Microglia shape the synaptic environment in health and disease, but synapses do not exist in a vacuum. Instead, pre- and postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise the four elements of the contemporary tetrapartite synapse model. While research in this area is still just beginning, accumulating evidence points toward a novel role for microglia in regulating the ECM during normal brain homeostasis, and such processes may, in turn, become dysfunctional in disease. As it relates to synapses, microglia are reported to modify the perisynaptic matrix, which is the diffuse matrix that surrounds dendritic and axonal terminals, as well as perineuronal nets (PNNs), specialized reticular formations of compact ECM that enwrap neuronal subsets and stabilize proximal synapses. The interconnected relationship between synapses and the ECM in which they are embedded suggests that alterations in one structure necessarily affect the dynamics of the other, and microglia may need to sculpt the matrix to modify the synapses within. Here, we provide an overview of the microglial regulation of synapses, perisynaptic matrix, and PNNs, propose candidate mechanisms by which these structures may be modified, and present the implications of such modifications in normal brain homeostasis and in disease.

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Sorted by citations

Authors
Crapser, J. D., Arreola, M. A., Tsourmas, K. I., & Green, K. N.
Affiliations
University of California, Irvine (US)
Corresponding author
Green, Kim N.
ORCID
Venue
Cellular & Molecular Immunology
Publisher
Springer Science and Business Media LLC
Published
2021-08-19
Volume
18
Issue
11
Pages
2472-2488
ISSN
  • 1672-7681 (ISSN-L)
  • 2042-0226
DOI
10.1038/s41423-021-00751-3
PMC
PMC8546068
OpenAlex
W3196214717
Cited by
178
References
90
Citations by year
2026: 37 · 2025: 48 · 2024: 43 · 2023: 26 · 2022: 21 · 2021: 2
FWCI
2.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute on Aging (RF1AG056768, RF1AG065329, U54 AG054349)
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (F31NS108611, F31NS111882)
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, extracellular matrix, synapses, perineuronal nets, synaptic regulation, brain homeostasis, neuroinflammation, glia
MeSH terms
Animals, Brain, Extracellular Matrix, Extracellular Space, Humans, Microglia, Immunological Synapses

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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