Etsuo A Susaki, Kazuki Tainaka, Dimitri Perrin, Fumiaki Kishino, Takehiro Tawara, Tomonobu M Watanabe, Chihiro Yokoyama, Hirotaka Onoe, Megumi Eguchi, Shun Yamaguchi, Takaya Abe, Hiroshi Kiyonari, Yoshihiro Shimizu, Atsushi Miyawaki, Hideo Yokota, Hiroki R Ueda (2014) Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis., Cell, Volume 157, Number 3, pp. 726-39
Published in 2014 Apr 24 (Electronic publication in April 17, 2014, midnight )
(Abstract) 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.(MeSH Terms)