Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord
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Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia–synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate–dependent protein kinase. Thus, we now provide a link between microglial activation and synaptic dysfunctions, which are common early features of many brain diseases.
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Inhibitory synapses in hippocampus appear to be unaffected by disruptions of neuron-microglia signaling.
“Notably, inhibitory synapses in hippocampus appear to be unaffected by disruptions of neuron–microglia signaling11 (but see ref. 13).”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [13]
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- Authors
- Cantaut-Belarif, Y., Antri, M., Pizzarelli, R., Colasse, S., Vaccari, I., Soares, S., Renner, M., Dallel, R., Triller, A., & Bessis, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Corresponding author
- Bessis, Alain
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2017-07-17
- Volume
- 216
- Issue
- 9
- Pages
- 2979-2989
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC5584146
- OpenAlex
- W2736215336
- Cited by
- 56
- References
- 64
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 11 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 10 · 2017: 2
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche
- H2020 European Research Council
- Investissements d’Avenir (ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL Research University)
- Fondation pour la Recherche Médicale (FDT20130928360, DGE20111123023)
- Région Ile-de-France (NERF 2009-44, NERF 2011-45)
- Fédération pour la Recherche sur le Cerveau (2011)
- France BioImaging (ANR-10-INSB-04-01)
- Institut national de la santé et de la recherche médicale
- Clermont Université
- Région Auvergne
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- microglia, glycinergic synapses, GABAergic synapses, prostaglandin E2, glycine receptor, GABAA receptor, activity-dependent synaptic plasticity, EP2 receptor, protein kinase A, inhibitory neurotransmission, spinal cord
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Diffusion, Female, gamma-Aminobutyric Acid, Glycine, Male, Membrane Potentials, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Neural Inhibition, Synaptic Transmission, Receptors, GABA-A, Spinal Cord, Synaptic Membranes, Time Factors, Dinoprostone, Microglia, Cyclic AMP-Dependent Protein Kinases, Receptors, Glycine, Protein Transport, Tissue Culture Techniques, Electrical Synapses, Receptors, Prostaglandin E, EP2 Subtype
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