Journal
NATURE NEUROSCIENCE
Volume 21, Issue 4, Pages 625-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0109-1
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Funding
- AMED-CREST (AMED/MEXT) [JP17gm0610006]
- CREST (JST/MEXT)
- Brain/MINDS (AMED/MEXT) [JP17dm0207049]
- Basic Science and Platform Technology Program for Innovative Biological Medicine (AMED/MEXT) [JP17am0301025]
- Translational Research Network Program from Japan Agency for Medical Research and development (AMED)
- World Premier International Research Center Initiative (MEXT)
- JSPS KAKENHI [16J05041, 25221004, 16K15124, 23115006, 15H01558, 17H05688]
- Naito Foundation
- Grants-in-Aid for Scientific Research [17H05700, 16J05041, 17H05688, 16H01621, 25117002, 17H06062, 16K15124, 15H01558] Funding Source: KAKEN
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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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