Selective activation of microglia facilitates synaptic strength
Open accessAbstract
Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1β from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.
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Activation of the fractalkine receptor (CX3CR1) in microglial cells increases synaptic strength; deficiency in this receptor results in reduced hippocampal synaptic plasticity.
“The activation of the fractalkine receptor (CX3CR1) in microglial cells, increases synaptic strength. However, deficiency in this receptor results in a reduced hippocampal synaptic plasticity (Rogers et al., 2011; Clark et al., 2015).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Clark et al., 2015
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- Authors
- Clark, A. K., Gruber-Schoffnegger, D., Drdla-Schutting, R., Gerhold, K. J., Malcangio, M., & Sandkühler, J.
- Affiliations
- King's College London (GB)
- Medical University of Vienna (AT)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-03-18
- Volume
- 35
- Issue
- 11
- Pages
- 4552-4570
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4363384
- OpenAlex
- W2063244116
- Cited by
- 171
- References
- 65
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 18 · 2021: 23 · 2020: 14 · 2019: 15 · 2018: 18 · 2017: 12 · 2016: 18 · 2015: 9
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (093173/Z/10/Z)
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, synaptic plasticity, synaptic facilitation, CX3CR1, fractalkine, IL-1β, eicosanoids, presynaptic neurotransmitter release, nociceptive pathways, dorsal horn, C-fibers, pain amplification, chronic pain, glial cells
- MeSH terms
- Animals, Male, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Spinal Cord, Rats, Sprague-Dawley, Microglia, Excitatory Postsynaptic Potentials, Rats
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