A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing

Tatsuya C. Murakami, Tomoyuki Mano, Shu Saikawa, Shuhei A. Horiguchi, Daichi Shigeta, Kousuke Baba, Hiroshi Sekiya, Yoshihiro Shimizu, Kenji Tanaka, Hiroshi Kiyonari, Masamitsu Iino, Hideki Mochizuki, Kazuki Tainaka, Hiroki R. Ueda

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49 Citations (Scopus)

Abstract

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalNature Neuroscience
DOIs
Publication statusAccepted/In press - 2018 Mar 5

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Murakami, T. C., Mano, T., Saikawa, S., Horiguchi, S. A., Shigeta, D., Baba, K., Sekiya, H., Shimizu, Y., Tanaka, K., Kiyonari, H., Iino, M., Mochizuki, H., Tainaka, K., & Ueda, H. R. (Accepted/In press). A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing. Nature Neuroscience, 1-13. https://doi.org/10.1038/s41593-018-0109-1