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

被引：202

作者：

Murakami, Tatsuya C. ^{[1
]}

Mano, Tomoyuki ^{[1
,2
]}

Saikawa, Shu ^{[3
]}

Horiguchi, Shuhei A. ^{[4
,5
]}

Shigeta, Daichi ^{[1
]}

Baba, Kousuke ^{[6
,7
]}

Sekiya, Hiroshi ^{[8
]}

Shimizu, Yoshihiro ^{[9
]}

Tanaka, Kenji F. ^{[10
]}

Kiyonari, Hiroshi ^{[11
,12
]}

Iino, Masamitsu ^{[8
,13
]}

Mochizuki, Hideki ^{[6
]}

Tainaka, Kazuki ^{[1
,14
]}

Ueda, Hiroki R. ^{[1
,2
,4
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Syst Pharmacol, Tokyo, Japan

[2] Univ Tokyo, WPI IRCN, UTIAS, Tokyo, Japan

[3] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Chiba, Japan

[4] RIKEN, Quantitat Biol Ctr, Lab Synthet Biol, Osaka, Japan

[5] Osaka Univ, Sch Engn Sci, Dept Syst Sci, Osaka, Japan

[6] Osaka Univ, Dept Neurol, Grad Sch Med, Osaka, Japan

[7] Osaka Univ, Grad Sch Med, Dept Kampo Med, Osaka, Japan

[8] Univ Tokyo, Grad Sch Med, Dept Pharmacol, Tokyo, Japan

[9] RIKEN, Quantitat Biol Ctr, Lab Cell Free Prot Synth, Osaka, Japan

[10] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan

[11] RIKEN, Ctr Life Sci Technol, Anim Resource Dev Unit, Kobe, Hyogo, Japan

[12] RIKEN, Ctr Life Sci Technol, Genet Engn Team, Kobe, Hyogo, Japan

[13] Nihon Univ, Sch Med, Div Cellular & Mol Pharmacol, Tokyo, Japan

[14] Niigata Univ, Brain Res Inst, Niigata, Japan

来源：

NATURE NEUROSCIENCE | 2018年 / 21卷 / 04期

关键词：

WAXHOLM SPACE; SCALING RULES; BODY; RECONSTRUCTION; VISUALIZATION; ACTIVATION; VERSATILE; ORGANS;

D O I：

10.1038/s41593-018-0109-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：625 / +

页数：18