Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis

被引:945
|
作者
Susaki, Etsuo A. [1 ,2 ,3 ,4 ]
Tainaka, Kazuki [1 ,3 ,4 ]
Perrin, Dimitri [2 ]
Kishino, Fumiaki [5 ]
Tawara, Takehiro [6 ]
Watanabe, Tomonobu M. [7 ]
Yokoyama, Chihiro [8 ]
Onoe, Hirotaka [8 ]
Eguchi, Megumi [9 ]
Yamaguchi, Shun [9 ,10 ]
Abe, Takaya [11 ]
Kiyonari, Hiroshi [11 ]
Shimizu, Yoshihiro [12 ]
Miyawaki, Atsushi [13 ]
Yokota, Hideo [6 ]
Ueda, Hiroki R. [1 ,2 ,3 ,4 ]
机构
[1] RIKEN Quantitat Biol Ctr, Lab Synthet Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan
[2] RIKEN Ctr Dev Biol, Lab Syst Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan
[3] Univ Tokyo, Grad Sch Med, Dept Syst Pharmacol, Bunkyo Ku, Tokyo 1130033, Japan
[4] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan
[5] Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 1130033, Japan
[6] RIKEN Ctr Adv Photon, Image Proc Res Team, Wako, Saitama 3510198, Japan
[7] Osaka Univ, OLABB, RIKEN Quantitat Biol Ctr, Lab Comprehens Bioimaging, Suita, Osaka 5650874, Japan
[8] RIKEN Ctr Life Sci Technol, Biofunct Imaging Team, Chuo Ku, Kobe, Hyogo 6500047, Japan
[9] Gifu Univ, Grad Sch Med, Div Morphol Neurosci, Gifu 5011194, Japan
[10] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
[11] RIKEN Ctr Dev Biol, Lab Anim Resources & Genet Engn, Chuo Ku, Kobe, Hyogo 6500047, Japan
[12] RIKEN Quantitat Biol Ctr, Lab Cell Free Prot Synth, Chuo Ku, Kobe, Hyogo 6500047, Japan
[13] RIKEN Brain Sci Inst, Lab Cell Funct Dynam, Wako, Saitama 3510198, Japan
基金
日本学术振兴会; 日本科学技术振兴机构;
关键词
LIGHT-SHEET MICROSCOPY; MOUSE-BRAIN; IN-VIVO; ULTRAMICROSCOPY; RECONSTRUCTION; CONNECTIONS; PROJECTIONS; EXPRESSION; MICE; VISUALIZATION;
D O I
10.1016/j.cell.2014.03.042
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution.
引用
收藏
页码:726 / 739
页数:14
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