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Cited by 61Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchConnexins and lens biology

Microglia maintain the normal structure and function of the hippocampal astrocyte network

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Du, Yixing, Brennan, Faith H., Popovich, Phillip G., Zhou, Min·2022·Glia
DOI 10.1002/glia.24179PMC PMC9324808
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Abstract

Microglial control of activity‐dependent plasticity and synaptic remodeling in neuronal networks has been the subject of intense research in the past several years. Although microglia–neuron interactions have been extensively studied, less is known about how microglia influence astrocyte‐dependent control over neuronal structure and function. Here, we explored a role for microglia in regulating the structure and function of the astrocyte syncytium in mouse hippocampus. After depleting microglia using a CSF1R antagonist (PLX5622, Plexxikon), we observed severe disruption of astrocyte syncytial isopotentiality and dye coupling. A decrease in astrocyte‐specific gap junction connexin (Cx) 30 and 43 expression, at least partially accounts for these microglia‐dependent changes in astrocytes. Because neuronal function requires intact astrocyte coupling, we also evaluated the effects of microglia depletion on synaptic transmission in the hippocampus. Without microglia, the strength of synaptic transmission was reduced at baseline and after long‐term potentiation (LTP). Conversely, priming microglia with systemic injections of lipopolysaccharide enhanced CA3‐CA1 synaptic transmission. This microglia‐induced scaling of synaptic transmission was associated with increased expression of post‐synaptic scaffold proteins (Homer1) in CA1. However, astrocyte network function was not affected by microglia priming, indicating that microglia‐dependent effects on astrocytes and neurons vary across functional states. Through manipulation of microglia in the brain, our results reveal the importance of microglia in homeostatic regulation of the astrocyte syncytium and scaling of synaptic transmission. These novel mechanisms uncover a new direction for future studies interrogating microglia function in various physiological and pathological contexts.

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Cited by

Sorted by citations

Authors
Du, Y., Brennan, F. H., Popovich, P. G., & Zhou, M.
Affiliations
The Ohio State University Wexner Medical Center (US)
Corresponding author
  • Popovich, Phillip G.
  • Zhou, Min
ORCID
Venue
Glia
Publisher
Wiley
Published
2022-04-08
Volume
70
Issue
7
Pages
1359-1379
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
DOI
10.1002/glia.24179
PMC
PMC9324808
OpenAlex
W4224283842
Cited by
61
References
13
Citations by year
2026: 10 · 2025: 10 · 2024: 16 · 2023: 21 · 2022: 4
FWCI
4.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Glia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01NS099532, R01NS083942, R35NS111582, RO1NS116059)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords
microglia, astrocytes, electrical coupling, connexin 30, connexin 43, PLX5622, microglia depletion, synaptic transmission, long-term potentiation, Homer1, lipopolysaccharide, hippocampus, CA1, CA3, astrocyte-neuron interaction, homeostatic regulation
MeSH terms
Connexin 30, Animals, Astrocytes, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Microglia, Long-Term Potentiation, Mice

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