Faculty, Staff and Student Publications
Language
English
Publication Date
2-28-2025
Journal
Science Advances
DOI
10.1126/sciadv.ado7829
PMID
40020068
PMCID
PMC11870068
PubMedCentral® Posted Date
2-28-2025
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Microglia, Animals, Neurons, Signal Transduction, Mice, Designer Drugs, Receptors, G-Protein-Coupled, GTP-Binding Protein alpha Subunits, Gi-Go, Brain, Mice, Inbred C57BL, Chemogenetics
Published Open-Access
yes
Recommended Citation
Zhao, Shunyi; Wang, Lingxiao; Kleidonas, Dimitrios; et al., "Chemogenetic Activation of Microglial Gi Signaling Decreases Microglial Surveillance and Impairs Neuronal Synchronization" (2025). Faculty, Staff and Student Publications. 3356.
https://digitalcommons.library.tmc.edu/uthmed_docs/3356