Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission
Open accessAbstract
Fine control of neuronal activity is crucial to rapidly adjust to subtle changes of the environment. This fine tuning was thought to be purely neuronal until the discovery that astrocytes are active players of synaptic transmission. In the adult hippocampus, microglia are the other major glial cell type. Microglia are highly dynamic and closely associated with neurons and astrocytes. They react rapidly to modifications of their environment and are able to release molecules known to control neuronal function and synaptic transmission. Therefore, microglia display functional features of synaptic partners, but their involvement in the regulation of synaptic transmission has not yet been addressed. We have used a combination of pharmacological approaches with electrophysiological analysis on acute hippocampal slices and ATP assays in purified cell cultures to show that activation of microglia induces a rapid increase of spontaneous excitatory postsynaptic currents. We found that this modulation is mediated by binding of ATP to P2Y1R located on astrocytes and is independent of TNFα or NOS2. Our data indicate that, on activation, microglia cells rapidly release small amounts of ATP, and astrocytes, in turn, amplified this release. Finally, P2Y1 stimulation of astrocytes increased excitatory postsynaptic current frequency through a metabotropic glutamate receptor 5-dependent mechanism. These results indicate that microglia are genuine regulators of neurotransmission and place microglia as upstream partners of astrocytes. Because pathological activation of microglia and alteration of neurotransmission are two early symptoms of most brain diseases, our work also provides a basis for understanding synaptic dysfunction in neuronal diseases.
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Microglia regulate astrocyte reactivity in disease.
“These data suggest that microglia regulate astrocyte reactivity in disease, fully consistent with previous reports19,20.”
From Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model (2019) · cites this paper as [20]
BG astrocytes are well positioned to participate in shaping baseline microglial phenotypes.
“suggest that BG astrocytes are well positioned to participate in shaping baseline microglial phenotypes.”
From Local cues establish and maintain region-specific phenotypes of basal ganglia microglia (2017) · cites this paper as Pascual et al., 2012
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Research works printed but not linked: 3
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- Authors
- Pascual, O., Ben Achour, S., Rostaing, P., Triller, A., & Bessis, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut de Biologie de l'Ecole Normale Supérieure, F-75005 Paris, France;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-13
- Volume
- 109
- Issue
- 4
- Pages
- E197-205
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3268269
- OpenAlex
- W2086400668
- Cited by
- 693
- References
- 88
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 45 · 2023: 43 · 2022: 67 · 2021: 57 · 2020: 68 · 2019: 44 · 2018: 51 · 2017: 43 · 2016: 46 · 2015: 52 · 2014: 55 · 2013: 43 · 2012: 14
- FWCI
- 20.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- microglial activation, astrocytes, excitatory neurotransmission, ATP release, P2Y1 receptor, metabotropic glutamate receptor 5, spontaneous excitatory postsynaptic currents, hippocampus, astrocyte-microglia interaction
- MeSH terms
- Adenosine Triphosphate, Analysis of Variance, Animals, Astrocytes, Electrophysiology, Fluorescent Antibody Technique, Hippocampus, Immunohistochemistry, Mice, Inbred C57BL, Microscopy, Electron, Blotting, Western, Microglia, DNA Primers, Receptors, Metabotropic Glutamate, Mice, Knockout, Microscopy, Confocal, Excitatory Postsynaptic Potentials, Mice, Receptors, Purinergic P2Y1, Real-Time Polymerase Chain Reaction, Receptor, Metabotropic Glutamate 5
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