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Updated: Jul 9, 2026

Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices
Published on: April 5, 2016
Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity
Min-Hee Yi1, Yi Liu2, Yong U Liu3
1Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun, Jeollanam-do 58128, Republic of Korea; Institute for Biomedical Science (IBS) of Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do 58128, Republic of Korea; BioMedical Sciences Graduate Program (BMSGP), Chonnam National University, Hwasun, Jeollanam-do 58128, Republic of Korea.
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.
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