Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain
Open accessAbstract
Microglia actively survey the brain microenvironment and play essential roles in sculpting synaptic connections during brain development. While microglial functions in the adult brain are less clear, activated microglia can closely appose neuronal cell bodies and displace axosomatic presynaptic terminals. Microglia-mediated stripping of presynaptic terminals is considered neuroprotective, but the cellular and molecular mechanisms are poorly defined. Using 3D electron microscopy, we demonstrate that activated microglia displace inhibitory presynaptic terminals from cortical neurons in adult mice. Electrophysiological recordings further establish that the reduction in inhibitory GABAergic synapses increased synchronized firing of cortical neurons in γ-frequency band. Increased neuronal activity results in the calcium-mediated activation of CaM kinase IV, phosphorylation of CREB, increased expression of antiapoptotic and neurotrophic molecules and reduced apoptosis of cortical neurons following injury. These results indicate that activated microglia can protect the adult brain by migrating to inhibitory synapses and displacing them from cortical neurons.
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Activated microglia migrate to inhibitory synapses and displace them from excitatory neurons.
“It has been reported that activated microglia migrate to inhibitory synapses and displace them from excitatory neurons [154]”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [154]
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“…activation and synaptic injury Neuronal injury correlates with microglial activation in MS gray matter (Magliozzi et al., 2010) and EAE hippocampus (Ziehn et al., 2010), but whether this activation triggers damage or may represent a protective response to it has been unclear (Chen et al., 2014).”
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- Authors
- Chen, Z., Jalabi, W., Hu, W., Park, H.-J., Gale, J. T., Kidd, G. J., Bernatowicz, R., Gossman, Z. C., Chen, J. T., Dutta, R., & Trapp, B. D.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Trapp, Bruce D.
- Venue
- Nature Communications
- Published
- 2014-07-22
- Volume
- 5
- Issue
- 1
- Pages
- 4486-4486
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4109015
- OpenAlex
- W2025921501
- Cited by
- 319
- References
- 50
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 27 · 2023: 23 · 2022: 36 · 2021: 35 · 2020: 34 · 2019: 30 · 2018: 23 · 2017: 23 · 2016: 21 · 2015: 18 · 2014: 6
- FWCI
- 11.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Multiple Sclerosis Society
- Multiple Sclerosis Society of Canada
- Multiple Sclerosis Society
- 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, inhibitory synapses, neuroprotection, GABAergic synapses, cortical neurons, microglial activation, CREB phosphorylation, neuronal apoptosis, neurotrophic factors, gamma oscillations, neuronal synchronization, brain injury, adult brain
- MeSH terms
- Animals, Brain, Cerebral Cortex, Electrophysiology, gamma-Aminobutyric Acid, Lipopolysaccharides, Male, Mice, Inbred C57BL, Microscopy, Electron, Neurons, Phosphorylation, Synapses, Rats, Sprague-Dawley, Apoptosis, Cyclic AMP Response Element-Binding Protein, Microglia, Presynaptic Terminals, Imaging, Three-Dimensional, Calcium-Calmodulin-Dependent Protein Kinase Type 4
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