Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity
Issued Date
2025-05-27
Resource Type
ISSN
26391856
eISSN
22111247
Scopus ID
2-s2.0-105004987459
Journal Title
Cell Reports
Volume
44
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cell Reports Vol.44 No.5 (2025)
Suggested Citation
Yi M.H., Liu Y., Liu Y.U., Lee J., Hanumaihgari P., Parusel S., Bosco D.B., Wang L., Zheng J., Shi W., Eauchai L., Chompoopong S., Hunt C.L., Wu L.J. Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity. Cell Reports Vol.44 No.5 (2025). doi:10.1016/j.celrep.2025.115717 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110268
Title
Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity
Author's Affiliation
Chonnam National University Hwasun Hospital
Siriraj Hospital
The First Affiliated Hospital, Sun Yat-sen University
South China University of Technology
McGovern Medical School
Chonnam National University Medical School
Chonnam National University
Mayo Clinic
Johns Hopkins Medical Institutions
Mayo Clinic in Jacksonville, Florida
Siriraj Hospital
The First Affiliated Hospital, Sun Yat-sen University
South China University of Technology
McGovern Medical School
Chonnam National University Medical School
Chonnam National University
Mayo Clinic
Johns Hopkins Medical Institutions
Mayo Clinic in Jacksonville, Florida
Corresponding Author(s)
Other Contributor(s)
Abstract
Chronic pain following peripheral nerve injury is accompanied by increased neuronal activity in the somatosensory cortex. However, whether and how cortical microglia contribute to these changes is less understood. To this end, we applied an optogenetic strategy to specifically target cortical microglia and investigate their function in behavioral pain sensitization. We found that optogenetic activation of microglia in the primary somatosensory cortex (S1) via red-activated channelrhodopsin (ReaChR) triggered pain hypersensitivity and affective-motivational responses in mice. Remarkably, S1-targeted optogenetic stimulation increased microglial landscape changes and ATP release. In addition, optogenetic stimulation altered the microglial proteomic profile, upregulated neuronal c-Fos expression, and enhanced neuronal Ca2+ signaling in the S1. Our results provide mechanistic evidence linking cortical microglia with neuronal hyperactivity and chronic pain behaviors.