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

Murakami, Tatsuya C., Mano, Tomoyuki, Saikawa, Shu, Horiguchi, Shuhei A., Shigeta, Daichi, Baba, Kousuke, Sekiya, Hiroshi, Shimizu, Yoshihiro, Tanaka, Kenji F., Kiyonari, Hiroshi, Iino, Masamitsu, Mochizuki, Hideki, Tainaka, Kazuki, Ueda, Hiroki R.·2018·Nature Neuroscience

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.

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Metadata

Authors
Murakami, T. C., Mano, T., Saikawa, S., Horiguchi, S. A., Shigeta, D., Baba, K., Sekiya, H., Shimizu, Y., Tanaka, K. F., Kiyonari, H., Iino, M., Mochizuki, H., Tainaka, K., & Ueda, H. R.
Venue
Nature Neuroscience
Published
2018-03-05
Volume
21
Issue
4
Pages
625-637
ISSN
  • 1097-6256
  • 1546-1726
Cited by
292
References
10
Language
en

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