Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity
Summary: 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 cortic...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004887 |
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| author | Min-Hee Yi Yi Liu Yong U. Liu Jinkyung Lee Priyanka Hanumaihgari Sebastian Parusel Dale B. Bosco Lingxiao Wang Jiaying Zheng Wu Shi Lattawat Eauchai Supin Chompoopong Christine L. Hunt Long-Jun Wu |
| author_facet | Min-Hee Yi Yi Liu Yong U. Liu Jinkyung Lee Priyanka Hanumaihgari Sebastian Parusel Dale B. Bosco Lingxiao Wang Jiaying Zheng Wu Shi Lattawat Eauchai Supin Chompoopong Christine L. Hunt Long-Jun Wu |
| author_sort | Min-Hee Yi |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-86ab34fac7f8486d9a5d01dfc1b68025 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-86ab34fac7f8486d9a5d01dfc1b680252025-08-20T03:49:41ZengElsevierCell Reports2211-12472025-05-0144511571710.1016/j.celrep.2025.115717Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivityMin-Hee Yi0Yi Liu1Yong U. Liu2Jinkyung Lee3Priyanka Hanumaihgari4Sebastian Parusel5Dale B. Bosco6Lingxiao Wang7Jiaying Zheng8Wu Shi9Lattawat Eauchai10Supin Chompoopong11Christine L. Hunt12Long-Jun Wu13Department 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 KoreaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA; Department of Anesthesiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, ChinaDepartment of Anesthesiology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaBioMedical Sciences Graduate Program (BMSGP), Chonnam National University, Hwasun, Jeollanam-do 58128, Republic of KoreaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Neuroscience, Johns Hopkins Medical Institute, Baltimore, MD 21205, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandFaculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Pain Medicine, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725004887CP: Neuroscience |
| spellingShingle | Min-Hee Yi Yi Liu Yong U. Liu Jinkyung Lee Priyanka Hanumaihgari Sebastian Parusel Dale B. Bosco Lingxiao Wang Jiaying Zheng Wu Shi Lattawat Eauchai Supin Chompoopong Christine L. Hunt Long-Jun Wu Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity Cell Reports CP: Neuroscience |
| title | Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity |
| title_full | Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity |
| title_fullStr | Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity |
| title_full_unstemmed | Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity |
| title_short | Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity |
| title_sort | optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004887 |
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