Link Brain-Wide Projectome to Neuronal Dynamics in the Mouse Brain

 Xiang Li1,2,3 · Yun Du4,5 · Jiang‑Feng Huang1,2,3 · Wen‑Wei Li1,2 · Wei Song4,6 · Ruo‑Nan Fan1,2,3 · Hua Zhou4  · Tao Jiang7  · Chang‑Geng Lu1,2,3 · Zhuang Guan1,2 · Xiao‑Fei Wang4  · Hui Gong1,2,7 · Xiang‑Ning Li7,8 · Anan Li1,2,7 · Ling Fu1,2,3,8,9 · Yan‑Gang Sun4
1 Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China 
2 MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China 
3 Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China 
4 Institute of Neuroscience, Key Laboratory of Brain Coginition and Brain-inspired Intelligence Technology, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 
5 University of Chinese Academy of Sciences, Beijing 100049, China 
6 School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China 
7 HUST-Suzhou Institute for Brainsmatics, JITRI Institute for Brainsmatics, Suzhou 215123, China 
8 School of Biomedical Engineering, Hainan University, Haikou 570228, China 9 School of Physics and Optoelectronics Engineering, Hainan University, Haikou 570228, Hainan, China

Abstract
Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

Keywords
In vivo imaging; fMOST; AO imaging; Deep brain regions