ArticleScience advances2025
Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Gq Signaling in Microglia Triggers Interferon Responses and Improves Outcome After Ischemic Stroke.Glia · 2026Article
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Microglial Deubiquitinase OTUD7B Stabilizes STAT3 to Promote Neuroinflammation and Cognitive Decline in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neuroimmune regulation of visceral pain: roles of microglia, purinergic signaling, and neuroinflammation.Frontiers in immunology · 2026Review
- Satellite microglia gate neuronal excitability by shielding inhibitory synapses in adult brain.bioRxiv : the preprint server for biology · 2025Article
- Microglia-to-neuron signaling linksProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cutting-edge technologies in neural regeneration.Cell regeneration (London, England) · 2025Review
- Microglia-to-neuron signaling increases lipid droplet metabolism, enhancing neuronal network activity.bioRxiv : the preprint server for biology · 2025Article
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8 authors.
Funding
Abstract
Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi protein-coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we used Gi-based designer receptors exclusively activated by designer drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Together, this study demonstrates that acute, exogenous activation of microglial Gi signaling regulates neuronal circuit function, offering a potential pharmacological target for the neuromodulation through microglia.
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