Microglia Function in Central Nervous System Development and Plasticity
Open accessAbstract
The nervous system comprises a remarkably diverse and complex network of different cell types, which must communicate with one another with speed, reliability, and precision. Thus, the developmental patterning and maintenance of these cell populations and their connections with one another pose a rather formidable task. Emerging data implicate microglia, the resident myeloid-derived cells of the central nervous system (CNS), in the spatial patterning and synaptic wiring throughout the healthy, developing, and adult CNS. Importantly, new tools to specifically manipulate microglia function have revealed that these cellular functions translate, on a systems level, to effects on overall behavior. In this review, we give a historical perspective of work to identify microglia function in the healthy CNS and highlight exciting new work in the field that has identified roles for these cells in CNS development, maintenance, and plasticity.
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Microglia are macrophage-like cells that comprise 10-15% of the CNS and mediate diverse functions ranging from innate immunity and phagocytosis to synaptic pruning and the regulation of synaptic activity.
“Microglia are macrophage-like cells that comprise 10–15% of the CNS, and mediate diverse functions ranging from innate immunity and phagocytosis to synaptic pruning and the regulation of synaptic activity [416,417].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [417]
Activation of microglia through genetic, infectious, inflammatory, or physical stimuli leads to stereotypical changes in their morphology, accompanied by proliferation, migration, and the release of proinflammatory cytokines and chemokines.
“Activation of microglia through genetic, infectious, inflammatory, or physical stimuli, leads to stereotypical changes in their morphology, accompanied by proliferation, migration, and the release of proinflammatory cytokines and chemokines [417–419].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [417]
Microglia are the resident macrophage population of the central nervous system that perform functions required for typical development, homeostasis, plasticity, immunity and repair.
“Microglia are the resident macrophage population of the central nervous system (CNS) that perform functions required for typical development, as well as homeostasis, plasticity, immunity and repair (1–5).”
From An environment-dependent transcriptional network specifies human microglia identity (2017) · cites this paper as [4]
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Synapse elimination during development and disease: immune molecules take centre stage
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An Engulfment Assay: A Protocol to Assess Interactions Between CNS Phagocytes and Neurons
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Self-citationA behavioural characterization of neonatal infection-facilitated memory impairment in adult rats
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The morphogenesis of the zebrafish eye, including a fate map of the optic vesicle
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Neuroglial Activation and Neuroinflammation in the Brain of Patients With Autism
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Targeting synapses and myelin in the prevention of schizophrenia
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How Many Cell Types Does It Take to Wire a Brain?
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The Developing Nervous System*
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
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Self-citationMicroglia emerge as central players in brain disease
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Self-citationAn environment-dependent transcriptional network specifies human microglia identity
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Microglial signatures and their role in health and disease
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Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
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The microbiome: a key regulator of stress and neuroinflammation
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TREM2, microglia, and neurodegenerative diseases
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“Furthermore, gut microbiota may modulate CNS microglia maturation and functioning and thus also affect neural circuitry of the developing brain (228, 229).”
BackgroundMicroglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
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Microglia in Health and Disease
Ransohoff, R. M., & Khoury, J. E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020560 · Cited by 303 · see citing works
Glia in mammalian development and disease
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Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes
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Microbes, immunity, and behavior: psychoneuroimmunology meets the microbiome
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A Map of Transcriptional Heterogeneity and Regulatory Variation in Human Microglia
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“pruning and the regulation of synaptic activity [416,417].”
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Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia
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An updated assessment of microglia depletion: current concepts and future directions
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Environment matters: microglia function and dysfunction in a changing world
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Gut microbiota–driven brain Aβ amyloidosis in mice requires microglia
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Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins
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Implications of Microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
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Primary cilia-mediated regulation of microglial secretion in Alzheimer’s disease
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- Authors
- Schafer, D. P., & Stevens, B.
- Affiliations
- Boston Children's Hospital (US)
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-07-17
- Volume
- 7
- Issue
- 10
- Pages
- a020545
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC4588063
- OpenAlex
- W2151003930
- Cited by
- 353
- References
- 145
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 45 · 2023: 33 · 2022: 40 · 2021: 43 · 2020: 36 · 2019: 35 · 2018: 26 · 2017: 30 · 2016: 16 · 2015: 5
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- Dana Foundation
- Richard and Susan Smith Family Foundation
- National Institutes of Health (1f32ns066698-01a1)
- National Institute of Mental Health (K99MH102351)
- National Institute of Neurological Disorders and Stroke (R01-NS-07100801, R01NS071008, F32-NS-066698)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, central nervous system development, synaptic plasticity, myeloid-derived cells, behavior, brain development
- MeSH terms
- Animals, Behavior, Animal, Cell Differentiation, Cell Survival, Central Nervous System, Disease Models, Animal, Humans, Macrophages, Models, Neurological, Neuronal Plasticity, Cell Death, Microglia, Gene Expression Regulation, Developmental, Body Patterning, Myeloid Cells, Organogenesis, Cell Proliferation, Mice, Rats
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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.
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