title: Scale: a chemical approach for fluorescence imaging and reconstruction of             transparent mouse brain.
abstract: Optical methods for viewing neuronal populations and projections in the intact                 mammalian brain are needed, but light scattering prevents imaging deep into brain                 structures. We imaged fixed brain tissue using Scale, an aqueous reagent that                 renders biological samples optically transparent but completely preserves                 fluorescent signals in the clarified structures. In Scale-treated mouse                 brain, neurons labeled with genetically encoded fluorescent proteins were visualized                 at an unprecedented depth in millimeter-scale networks and at subcellular                 resolution. The improved depth and scale of imaging permitted comprehensive                 three-dimensional reconstructions of cortical, callosal and hippocampal projections                 whose extent was limited only by the working distance of the objective lenses. In                 the intact neurogenic niche of the dentate gyrus, Scale allowed the                 quantitation of distances of neural stem cells to blood vessels. Our findings                 suggest that the Scale method will be useful for light microscopy-based                 connectomics of cellular networks in brain and other tissues.
authors: Brain Science Institute, RIKEN, Wako-city,                     Saitama, Japan.
authors: Hiroshi
authors: H
authors: Hama
authors: Hiroshi
authors: H
authors: Kurokawa
authors: Hiroyuki
authors: H
authors: Kawano
authors: Ryoko
authors: R
authors: Ando
authors: Tomomi
authors: T
authors: Shimogori
authors: Hisayori
authors: H
authors: Noda
authors: Kiyoko
authors: K
authors: Fukami
authors: Asako
authors: A
authors: Sakaue-Sawano
authors: Atsushi
authors: A
authors: Miyawaki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D005990:Glycerol / Q000378:metabolism / Q000494:pharmacology; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017830:Octoxynol / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D018800:Thy-1 Antigens; D013997:Time Factors; D016707:Tissue Fixation / Q000379:methods*; D014508:Urea / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005990:Glycerol; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D017830:Octoxynol; D018091:Receptors, AMPA; D012794:Sialic Acids; D016708:Synaptophysin; D018800:Thy-1 Antigens; D014508:Urea; C577485:Nes protein, mouse; C568745:ScaleA2 solution; C103469:polysialyl neural cell adhesion molecule