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March 27, 2024
Luo’s Team latest finding: microglia regulates sleep through calcium-dependent modulation of norepinephrine transmission

On January 18, 2024, Luo Qingming, academician of the Chinese Academy of Sciences, and his team in School of Biomedical Engineering of Hainan University, published online a paper entitled microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission in Nature Neuroscience. This research was jointly conducted by Luo’s team and the team of Yang Dan, academician of Howard Hughes Medical Institute, University of California, Berkeley. With means of chemical genetics and pharmacology, the two teams have done in-depth exploration into the microglia's vital role in regulating sleep. The research findings indicate that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission.

Sleep disturbance is increasingly recognized as an important risk factor for Alzheimer's disease and other neurodegenerative diseases, while both sleep disturbances and microglia dysfunction have been implicated in multiple neurodegenerative diseases. The research reveals that microglia, the primary immune cells in the brain, have a key part in brain homeostasis by modulating neuronal activity, pruning synapses, and clearing cellular debris and harmful aggregates. 

The reconstruction and analysis of light-sheet microscopy-imaging data were completed by the team led by Luo Qingming, also president of Hainan University. As is well known, light sheet illumination microscopy-imaging has low axial resolution and susceptible to the interference of background fluorescence, which is difficult to be reconstructed, especially for the small size neuronal axon bouton with weak signal. In view of this problem, Luo's team proposed a weakly supervised deep learning method, which reduces the demand for annotated images through the iterative strategy, improving machine prediction accuracy and reducing the difficulty of morphological analysis of low-resolution and low SNR images. With this innovative approach, the team successfully completed the automatic identification and localization of 140 thousand boutons in mouse brains, verifying the spatial proximity between Iba1-labeled microglia and tyrosine hydroxylase (TH)+ axon bouton. This study provides a new perspective into the in-depth understanding of the neural mechanisms of sleep regulation, as well as offers an instructive probe into the application of information processing technology in the field of neuro-optical imaging.

The research team members include: Academician Luo Qingming, Professor Li An'an, Associate Professor Xiao Chi, Dr. Xu Zhengchao and Ph.D candidate Huang Ganghua participated in this research.

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Source from HNU News

Translated by Luo Hailin

Proofread by Chen Chuanxian, Yang Jie

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