Whole-Brain Imaging at the Single-Cell Resolution with the CUBIC Method — ASN Events
  1. Schedule
  2. High Performance & Supercomputing in Bioinformatics & Bioimaging
  3. Whole-Brain Imaging at the Single-Cell Resolution with the CUBIC Method

Whole-Brain Imaging at the Single-Cell Resolution with the CUBIC Method (#25)

Dimitri Perrin 1 , Etsuo A Susaki 1 2 3 4 , Kazuki Tainaka 2 3 4 , Hiroki R Ueda 1 2 3 4
  1. RIKEN Center for Developmental Biology, Kobe, Japan
  2. RIKEN Quantitative Biology Center, Kobe, Japan
  3. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  4. CREST, Japan Science and Technology Agency, Saitama, Japan

A major challenge of systems biology is to understand how emergent properties at the organism level result from specific phenomena at the cellular scale. This is particularly difficult (and crucial) in the brain, due to the complexity and importance of the organ. Whole-brain imaging has the potential to be a facilitating technology in these efforts, provided that it can operate at single-cell resolution and through a method with very high throughput. In this talk in the Highlights Track, we will present a method, called CUBIC (Clear, Unobstructed Brain Imaging Cocktails and Computational analysis), which we published this April [1].

CUBIC is the result of a comprehensive chemical screening, and 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. The method can be applied to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and it 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. All these elements, taken together, enable the visualization and quantification of neural activities induced by environmental stimulation.

In this presentation, we will explain the challenges associated with whole-brain imaging, as well as how CUBIC addresses limitations of previous methods and in doing so enables time-course expression profiling of whole adult brains with single-cell resolution. We will put particular emphasis on the computational challenges related to the handling and analysis of high-resolution 3D images.

  1. Susaki EA, Tainaka K, Perrin D, Kishino F, Tawara T, Watanabe TM, Yokoyama C, Onoe H, Eguchi M, Yamaguchi S, Abe T, Kiyonari H, Shimizu Y, Miyawaki A, Yokota H, Ueda HR. Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157(3):726-39, 2014. doi: 10.1016/j.cell.2014.03.042.