ArticleProceedings of the National Academy of Sciences of the United States of America2012
Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 379 papers.
What it found
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Who cites it
379 citing papers in PubMed, 679 citations in OpenAlex.
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- Prenatal stress alters offspring neurovascular, autonomic, and immune development in animal models of neuropsychiatric and cardiometabolic disorders.Journal of neuroendocrinology · 2026Review
- Amino acid modulation of the carotid body selectively modulates peripheral chemoreceptor respiratory reflex.The Journal of physiology · 2026Article
- Microglia-Dependent BDNF Signaling in the Dentate Gyrus Underlies the Antidepressant Effects of Gardiquimod, a Toll-Like Receptor 7 Agonist, in Chronically Stressed Mice.Neurochemical research · 2026Article
- Article
- Early microglial response to amyloid plaques drives sleep loss in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Cefepime Alleviates Comorbid Pain and Depression Induced by Lipopolysaccharide in Female Mice.Brain sciences · 2026Article
- Modulation of Glutamate Release by Dexmedetomidine Preserves Dendritic Spines and Alleviates Cognitive Impairment in a Murine Model of Perioperative Neurocognitive Disorder.Neuroscience bulletin · 2026Article
- The brain-heart axis: effects of cardiovascular disease on the CNS and opportunities for central neuromodulation.Nature reviews. Neuroscience · 2026Review
- Delivery of monoclonal antibodies to the brain: the impact of nanocarrier structure.Drug delivery and translational research · 2026Article
- Review
- 4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt.Neurochemical research · 2026Article
- Beta-lactam Antibiotic Cefepime Attenuates Lipopolysaccharide-induced Pain and Depression By Modulating Inflammatory Response and Astroglial Glutamate Transporter in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- Glucose metabolic reprogramming: mechanisms and therapeutic implications in neuroinflammation.Frontiers in immunology · 2026Review
- From Stress to Substance Use Disorders: The Expanding Role of Microglia-Astrocyte Crosstalk in Neuroimmune and Glutamate Alterations in the Nucleus Accumbens.International journal of molecular sciences · 2025Review
319 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.