Microglia: A new frontier for synaptic plasticity, learning and memory, and neurodegenerative disease research
Abstract
We focus on emerging roles for microglia in synaptic plasticity, cognition and disease. We outline evidence that ramified microglia, traditionally thought to be functionally "resting" (i.e. quiescent) in the normal brain, in fact are highly dynamic and plastic. Ramified microglia continually and rapidly extend processes, contact synapses in an activity and experience dependent manner, and play a functionally dynamic role in synaptic plasticity, possibly through release of cytokines and growth factors. Ramified microglial also contribute to structural plasticity through the elimination of synapses via phagocytic mechanisms, which is necessary for normal cognition. Microglia have numerous mechanisms to monitor neuronal activity and numerous mechanisms also exist to prevent them transitioning to an activated state, which involves retraction of their surveying processes. Based on the evidence, we suggest that maintaining the ramified state of microglia is essential for normal synaptic and structural plasticity that supports cognition. Further, we propose that change of their ramified morphology and function, as occurs in inflammation associated with numerous neurological disorders such as Alzheimer's and Parkinson's disease, disrupts their intricate and essential synaptic functions. In turn altered microglia function could cause synaptic dysfunction and excess synapse loss early in disease, initiating a range of pathologies that follow. We conclude that the future of learning and…
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Perturbations in homeostatic microglia functions at synapses may lead to early synapse loss in an Aβ-dependent or potentially independent manner.
“It is also suspected that perturbations in homeostatic microglia functions at synapses may lead to early synapse loss in an Aβ-dependent or potentially independent manner [52, 93].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [93]
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- Authors
- Morris, G. P., Clark, I. A., Zinn, R., & Vissel, B.
- Affiliations
- Garvan Institute of Medical Research (AU)
- Australian National University (AU)
- Corresponding author
- Vissel, Bryce
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 105
- Pages
- 40-53
- ISSN
- 1074-7427 (ISSN-L)
- OpenAlex
- W2041964216
- Cited by
- 236
- References
- 44
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 12 · 2023: 20 · 2022: 24 · 2021: 25 · 2020: 29 · 2019: 23 · 2018: 24 · 2017: 19 · 2016: 13 · 2015: 20 · 2014: 16 · 2013: 2
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- UTS ePRESS (University of Technology Sydney) (submittedVersion)
- 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, ramified microglia, synaptic plasticity, learning and memory, synaptic pruning, phagocytosis, microglial activation, neuroinflammation, Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, cytokine production, structural plasticity, non-neuronal cells
- MeSH terms
- Animals, Brain, Humans, Learning, Memory, Neuronal Plasticity, Microglia, Neurodegenerative Diseases, Mice, Rats
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