The DOI matches its Crossref record; 78 of the 79 references it cites were found in a registry or an index.
Microglial Interactions with Synapses Are Modulated by Visual Experience
Open accessAbstract
Microglia are the immune cells of the brain. In the absence of pathological insult, their highly motile processes continually survey the brain parenchyma and transiently contact synaptic elements. Aside from monitoring, their physiological roles at synapses are not known. To gain insight into possible roles of microglia in the modification of synaptic structures, we used immunocytochemical electron microscopy, serial section electron microscopy with three-dimensional reconstructions, and two-photon in vivo imaging to characterize microglial interactions with synapses during normal and altered sensory experience, in the visual cortex of juvenile mice. During normal visual experience, most microglial processes displayed direct apposition with multiple synapse-associated elements, including synaptic clefts. Microglial processes were also distinctively surrounded by pockets of extracellular space. In terms of dynamics, microglial processes localized to the vicinity of small and transiently growing dendritic spines, which were typically lost over 2 d. When experience was manipulated through light deprivation and reexposure, microglial processes changed their morphology, showed altered distributions of extracellular space, displayed phagocytic structures, apposed synaptic clefts more frequently, and enveloped synapse-associated elements more extensively. While light deprivation induced microglia to become less motile and changed their preference of localization to the vicinity of a subset of larger dendritic spines that persistently shrank, light reexposure reversed these behaviors. Taken together, these findings reveal different modalities of microglial interactions with synapses that are subtly altered by sensory experience. These findings suggest that microglia may actively contribute to the experience-dependent modification or elimination of a specific subset of synapses in the healthy brain.
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“Microglia have recently been implicated as active participants in brain plasticity per se (42–45).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [42]
In the citing paper
“microglia participate in experience-dependent remodeling of neural circuits in the normal mature brain by removing extraneous synaptic elements [6, 74–77]”
From Microglial dysfunction in brain aging and Alzheimer's disease (2014) · cites this paper as [74]
In the citing paper
“Microglia also closely monitor neural activity and regulate synaptic plasticity.”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Tremblay et al., 2010
In the citing paper
“Microglia dynamically interact with neuronal circuits, making direct contacts with synaptic elements1819 in a way that is modulated by experience-dependent changes in neuronal activity19.”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [19]
In the citing paper
“The motility of microglial processes and spine contact are actively regulated by sensory experience and are involved in spine elimination (Tremblay et al., 2010).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Tremblay et al., 2010
In the citing paper
“Another type of glial cells, microglia, have also been found to be in close contact with dendritic spines.”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Tremblay et al., 2010
In the citing paper
“The motility of microglial processes and spine contact are actively regulated by sensory experience and are involved in spine elimination (Tremblay et al., 2010).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Tremblay et al., 2010
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Cites
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The Classical Complement Cascade Mediates CNS Synapse Elimination
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Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
“To further confirm microglia-mediated phagocytosis of synaptic elements, immunohistochemical electron microscopy (immunoEM) for the microglia marker iba-1 was performed and quantified in the P5 dLGN (Figure 4C; Tremblay et al., 2010b).”
InfluentialKettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599
Microglial M1/M2 polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070
Metadata
- Authors
- Tremblay, M.-È., Lowery, R. L., & Majewska, A. K.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Tremblay, Marie-Ève
- Majewska, Ania K.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-11-02
- Volume
- 8
- Issue
- 11
- Pages
- e1000527
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC2970556
- OpenAlex
- W2066943555
- Cited by
- 1,542
- References
- 79
- Citations by year
- 2026: 62 · 2025: 74 · 2024: 127 · 2023: 90 · 2022: 122 · 2021: 145 · 2020: 127 · 2019: 149 · 2018: 107 · 2017: 97 · 2016: 101 · 2015: 95 · 2014: 103 · 2013: 66 · 2012: 48
- FWCI
- 27.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (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, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Burroughs Wellcome Fund
- Alfred P. Sloan Foundation
- University of Rochester
- Stiftung für die Erforschung der Muskelkrankheiten
- National Institutes of Health
- Medical Center, University of Rochester
- National Eye Institute (R01EY019277, EY019277)
- 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, synapses, visual cortex, sensory experience, light deprivation, dendritic spines, synaptic cleft, extracellular space, microglial motility, phagocytosis, experience-dependent synaptic plasticity, synaptic pruning, juvenile mice
- MeSH terms
- Animals, Extracellular Space, Microscopy, Electron, Synapses, Vision, Ocular, Microglia, Mice
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