Microglia contact induces synapse formation in developing somatosensory cortex
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Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8–10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca 2+ transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction.
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Microglia can elicit calcium transients and formation of filopodia from dendritic branches, and are required for learning-induced synapse formation.
“At the same time, studies have pointed to a role for microglia in synapse formation in the adult brain, showing that they can elicit calcium transients and the formation of filopodia from dendritic branches15, and that they are required for learning-induced synapse formation16.”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [15]
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“Microglia are in active and intimate association with neurons during key stages in development, which helps to shape neuronal connectivity (6, 9, 78, 79).”
- Authors
- Miyamoto, A., Wake, H., Ishikawa, A. W., Eto, K., Shibata, K., Murakoshi, H., Koizumi, S., Moorhouse, A. J., Yoshimura, Y., & Nabekura, J.
- Affiliations
- Japan Agency for Medical Research and Development (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Japan Science and Technology Agency (JP)
- UNSW Sydney (AU)
- Corresponding author
- Nabekura, Junichi
- ORCID
- Venue
- Nature Communications
- Published
- 2016-08-25
- Volume
- 7
- Issue
- 1
- Pages
- 12540-12540
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5007295
- OpenAlex
- W2509907732
- Cited by
- 649
- References
- 58
- Citations by year
- 2026: 31 · 2025: 58 · 2024: 90 · 2023: 66 · 2022: 84 · 2021: 97 · 2020: 65 · 2019: 78 · 2018: 45 · 2017: 32 · 2016: 2
- FWCI
- 28.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (53457, 15K15524, 15K18351, 25253017, 22240042, 16H04669)
- National Institute for Basic Biology
- Precursory Research for Embryonic Science and Technology
- 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, synaptogenesis, somatosensory cortex, dendritic filopodia, dendritic spines, microglial activation, calcium transients, actin accumulation, microglial ablation, layer 2/3 pyramidal neurons, neural circuit development, microglia-neuron interaction
- MeSH terms
- Animals, Dendrites, Female, Immune System, Male, Mice, Inbred C57BL, Mice, Transgenic, Pseudopodia, Somatosensory Cortex, Spine, Synapses, Microglia, Pyramidal Cells, Models, Animal, Microscopy, Fluorescence, Multiphoton, Mice, Neurogenesis
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