ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed.
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- Investigating the Role of Cortical Microglia in a Mouse Model of Viral Infection-Induced Seizures.eNeuro · 2026Article
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Mechanism of Microbiota-Gut-Brain in Perimenopausal Depression: An Inflammatory Perspective.Expert reviews in molecular medicine · 2025Review
- The effects of P2Y12 loss on microglial gene expression, dynamics, and injury response in the cerebellum and cerebral cortex.Brain, behavior, and immunity · 2025Article
- Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond.Journal of neuroimmunology · 2025Review
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- How microglia contribute to the induction and maintenance of neuropathic pain.Nature reviews. Neuroscience · 2025Review
- Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model.Journal of neuroinflammation · 2025Article
- The Dual Role of Microglia in Multiple Sclerosis and its Implications for Diagnostics and Repair.Current neuropharmacology · 2025Review
- Current perspectives on microglia-neuron communication in the central nervous system: Direct and indirect modes of interaction.Journal of advanced research · 2024Review
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Microglial process convergence onto injured axonal swellings, a human postmortem brain tissue study.Scientific reports · 2024Article
- The embryonic zebrafish brain is exclusively colonized byScience advances · 2024Article
- Microglial process convergence onto injured axonal swellings, a human postmortem brain tissue study.Research square · 2024Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Microglia are morphologically dynamic cells that rapidly extend their processes in response to various stimuli including extracellular ATP. In this study, we tested the hypothesis that stimulation of neuronal NMDARs trigger ATP release leading to communication with microglia. We used acute mouse hippocampal brain slices and two-photon laser scanning microscopy to study microglial dynamics and developed a novel protocol for fixation and immunolabeling of microglia processes. Similar to direct topical ATP application in vivo, short multiple applications of NMDA triggered transient microglia process outgrowth that was reversible and repeatable indicating that this was not due to excitotoxic damage. Stimulation of NMDAR was required as NMDAR antagonists, but not blockers of AMPA/kainate receptors or voltage-gated sodium channels, prevented microglial outgrowth. We report that ATP release, secondary to NMDAR activation, was the key mediator of this neuron-microglia communication as both blocking purinergic receptors and inhibiting hydrolysis of ATP to prevent locally generated gradients abolished outgrowth. Pharmacological and genetic analyses showed that the NMDA-triggered microglia process extension was independent of Pannexin 1, the ATP releasing channels, ATP release from astrocytes via connexins, and nitric oxide generation. Finally, using whole-cell patch clamping we demonstrate that activation of dendritic NMDAR on single neurons is sufficient to trigger microglia process outgrowth. Our results suggest that dendritic neuronal NMDAR activation triggers ATP release via a Pannexin 1-independent manner that induces outgrowth of microglia processes. This represents a novel uncharacterized form of neuron-microglial communication mediated by ATP.
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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.