title: Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution.
abstract: Revealing neural circuit mechanisms is critical for understanding brain functions. Significant progress in dissecting neural connections has been made using optical imaging with fluorescence labels, especially in dissecting local connections. However, acquiring and tracing brain-wide, long-distance neural circuits at the neurite level remains a substantial challenge. Here, we describe a whole-brain approach to systematically obtaining continuous neuronal pathways in a fluorescent protein transgenic mouse at a one-micron voxel resolution. This goal is achieved by combining a novel resin-embedding method for maintaining fluorescence, an automated fluorescence micro-optical sectioning tomography system for long-term stable imaging, and a digital reconstruction-registration-annotation pipeline for tracing the axonal pathways in the mouse brain. With the unprecedented ability to image a whole mouse brain at a one-micron voxel resolution, the long-distance pathways were traced minutely and without interruption for the first time. With advancing labeling techniques, our method is believed to open an avenue to exploring both local and long-distance neural circuits that are related to brain functions and brain diseases down to the neurite level.
authors: Britton Chance Center for Biomedical Photonics, Huazhong University of Science and Technology-Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China.
authors: Hui
authors: H
authors: Gong
authors: Shaoqun
authors: S
authors: Zeng
authors: Cheng
authors: C
authors: Yan
authors: Xiaohua
authors: X
authors: Lv
authors: Zhongqin
authors: Z
authors: Yang
authors: Tonghui
authors: T
authors: Xu
authors: Zhao
authors: Z
authors: Feng
authors: Wenxiang
authors: W
authors: Ding
authors: Xiaoli
authors: X
authors: Qi
authors: Anan
authors: A
authors: Li
authors: Jingpeng
authors: J
authors: Wu
authors: Qingming
authors: Q
authors: Luo
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D001921:Brain / Q000648:ultrastructure; D001931:Brain Mapping / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000648:ultrastructure*; D041622:Tomography, Optical / Q000379:methods*