| Title | Imaging microglia surveillance during sleep-wake cycles in freely behaving mice |
| Authors | Gu, Xiaochun Zhao, Zhong Chen, Xueli Zhang, Lifeng Fang, Huaqiang Zhao, Ting Ju, Shenghong Gao, Weizheng Qian, Xiaoyu Wang, Xianhua Zhang, Jue Cheng, Heping |
| Affiliation | PKU Nanjing Inst Translat Med, Nanjing Raygen Hlth, Nanjing, Peoples R China Southeast Univ, Natl Platform Med Engn Educ Integrat, Nanjing, Peoples R China Southeast Univ, Zhongda Hosp, Med Sch, Jiangsu Key Lab Mol & Funct Imaging,Dept Radiol, Nanjing, Peoples R China Southeast Univ, Med Sch, Dept Histol Embryol, Key Lab Dev Genes & Human Dis, Nanjing, Peoples R China Chinese Acad Med Sci, Inst Basic Med Sci, Sch Basic Med, Peking Union Med Coll, Beijing, Peoples R China Chinese Acad Med Sci, PKU Nanjing Inst Translat Med, Res Unit Mitochondria Brain Dis, Nanjing, Peoples R China Peking Univ, Acad Adv Interdisciplinary Study, Coll Engn, Beijing, Peoples R China Peking Univ, State Key Lab Membrane Biol, Beijing Key Lab Cardiometab Mol Med, Inst Mol Med,Peking Tsinghua Ctr Life Sci,Coll Fut, Beijing 100871, Peoples R China Peking Univ, Coll Future Technol, Peking Tsinghua Ctr Life Sci, Natl Biomed Imaging Ctr,State Key Lab Membrane Bio, Beijing, Peoples R China |
| Keywords | NOREPINEPHRINE NEURONS CELLS ATP |
| Issue Date | 22-Dec-2023 |
| Publisher | ELIFE |
| Abstract | Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles remains unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice. We uncovered fast and robust brain state-dependent changes in microglia surveillance, occurring in parallel with sleep dynamics and early-onset phagocytic microglial contraction during sleep deprivation stress. We also detected local norepinephrine fluctuation occurring in a sleep state-dependent manner. We showed that the locus coeruleus-norepinephrine system, which is crucial to sleep homeostasis, is required for both sleep state-dependent and stress-induced microglial responses and beta 2-adrenergic receptor signaling plays a significant role in this process. These results provide direct evidence that microglial surveillance is exquisitely tuned to signals and stressors that regulate sleep dynamics and homeostasis so as to adjust its varied roles to complement those of neurons in the brain. In vivo imaging with mTPM in freely behaving animals, as demonstrated here, opens a new avenue for future investigation of microglia dynamics and sleep biology in freely behaving animals. |
| URI | http://hdl.handle.net/20.500.11897/698104 |
| ISSN | 2050-084X |
| DOI | 10.7554/eLife.86749 |
| Indexed | SCI(E) |
| Appears in Collections: | 工学院 分子医学研究所 膜生物学国家重点实验室 生命科学学院 |
