High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases.

[1]  H. Dodt,et al.  3D-reconstruction of blood vessels by ultramicroscopy , 2009, Organogenesis.

[2]  Shaoqun Zeng,et al.  Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution , 2013, NeuroImage.

[3]  D. Weinberger,et al.  Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia , 2007, Molecular Psychiatry.

[4]  D. Sharp,et al.  The role of the posterior cingulate cortex in cognition and disease. , 2014, Brain : a journal of neurology.

[5]  T. Miyakawa,et al.  Increased Behavioral and Neuronal Responses to a Hallucinogenic Drug in PACAP Heterozygous Mutant Mice , 2014, PloS one.

[6]  J. Sebat,et al.  Duplications of the Neuropeptide Receptor VIPR2 Confer Significant Risk for Schizophrenia , 2011, Nature.

[7]  Tristan A. Chaplin,et al.  Contrasting patterns of cortical input to architectural subdivisions of the area 8 complex: a retrograde tracing study in marmoset monkeys. , 2013, Cerebral cortex.

[8]  H. Vaudry,et al.  Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery , 2009, Pharmacological Reviews.

[9]  Srinivas C. Turaga,et al.  Mapping social behavior-induced brain activation at cellular resolution in the mouse. , 2014, Cell reports.

[10]  Brent A. Vogt,et al.  Cytoarchitecture of mouse and rat cingulate cortex with human homologies , 2012, Brain Structure and Function.

[11]  Rajan P Kulkarni,et al.  Single-Cell Phenotyping within Transparent Intact Tissue through Whole-Body Clearing , 2014, Cell.

[12]  William R. Gray Roncal,et al.  Saturated Reconstruction of a Volume of Neocortex , 2015, Cell.

[13]  B. Bradley,et al.  Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor , 2011, Nature.

[14]  Atsushi Miyawaki,et al.  ScaleS: an optical clearing palette for biological imaging , 2015, Nature Neuroscience.

[15]  D L Rosene,et al.  Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents , 1987, The Journal of comparative neurology.

[16]  Cheuk Y. Tang,et al.  Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes , 2016, Cell.

[17]  Simultaneous neuron- and astrocyte-specific fluorescent marking. , 2015, Biochemical and biophysical research communications.

[18]  C. Colwell,et al.  Reductions in synaptic proteins and selective alteration of prepulse inhibition in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2) agonist , 2015, Psychopharmacology.

[19]  Y. Yoneda,et al.  In vivo activation of c-Jun N-terminal kinase signaling cascade prior to granule cell death induced by trimethyltin in the dentate gyrus of mice , 2004, Neuropharmacology.

[20]  Dimitri Perrin,et al.  Whole-Body Imaging with Single-Cell Resolution by Tissue Decolorization , 2014, Cell.

[21]  K. Deisseroth,et al.  CLARITY for mapping the nervous system , 2013, Nature Methods.

[22]  J. Miyazaki,et al.  Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  S. Kida,et al.  Microendophenotypes of Psychiatric Disorders: Phenotypes of Psychiatric Disorders at the Level of Molecular Dynamics, Synapses, Neurons, and Neural Circuits , 2015, Current molecular medicine.

[24]  Kenji F. Tanaka,et al.  Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. , 2012, Cell reports.

[25]  Kenji F Tanaka,et al.  Gene induction in mature oligodendrocytes with a PLP‐tTA mouse line , 2012, Genesis.

[26]  Karel Svoboda,et al.  A platform for brain-wide imaging and reconstruction of individual neurons , 2016, eLife.

[27]  K. Deisseroth,et al.  Advanced CLARITY for rapid and high-resolution imaging of intact tissues , 2014, Nature Protocols.

[28]  H. Seung,et al.  Serial two-photon tomography: an automated method for ex-vivo mouse brain imaging , 2011, Nature Methods.

[29]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[30]  E. Susaki,et al.  Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis , 2014, Cell.

[31]  Takeharu Nagai,et al.  Shift anticipated in DNA microarray market , 2002, Nature Biotechnology.

[32]  Misha B. Ahrens,et al.  Visualizing Whole-Brain Activity and Development at the Single-Cell Level Using Light-Sheet Microscopy , 2015, Neuron.

[33]  H. Hashimoto,et al.  An enriched environment ameliorates memory impairments in PACAP-deficient mice , 2014, Behavioural Brain Research.

[34]  K. Sripanidkulchai,et al.  The topography of the mesencephalic and pontine projections from the cingulate cortex of the rat , 1984, Brain Research.

[35]  Shaoqun Zeng,et al.  High-throughput dual-colour precision imaging for brain-wide connectome with cytoarchitectonic landmarks at the cellular level , 2016, Nature Communications.

[36]  I. Figiel,et al.  Trimethyltin-evoked apoptosis of murine hippocampal granule neurons is accompanied by the expression of interleukin-1beta and interleukin-1 receptor antagonist in cells of ameboid phenotype, the majority of which are NG2-positive , 2008, Brain Research Bulletin.

[37]  Stephan Saalfeld,et al.  Globally optimal stitching of tiled 3D microscopic image acquisitions , 2009, Bioinform..

[38]  Edmund R Hollis,et al.  Efficient retrograde neuronal transduction utilizing self-complementary AAV1. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[39]  Randolf Menzel,et al.  Three-Dimensional Reconstruction and Segmentation of Intact Drosophila by Ultramicroscopy , 2009, Front. Syst. Neurosci..

[40]  Aaron S. Andalman,et al.  Structural and molecular interrogation of intact biological systems , 2013, Nature.

[41]  Erik D Herzog,et al.  Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons , 2005, Nature Neuroscience.

[42]  Jeremy Freeman Open source tools for large-scale neuroscience , 2015, Current Opinion in Neurobiology.

[43]  P. Osten,et al.  Mapping brain circuitry with a light microscope , 2013, Nature Methods.

[44]  Shun Yamaguchi,et al.  In vivo and in vitro visualization of gene expression dynamics over extensive areas of the brain , 2009, NeuroImage.

[45]  Dimitri Perrin,et al.  Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging , 2015, Nature Protocols.

[46]  Allan R. Jones,et al.  A mesoscale connectome of the mouse brain , 2014, Nature.

[47]  C. Colwell,et al.  Vasoactive intestinal peptide and the mammalian circadian system. , 2007, General and comparative endocrinology.

[48]  R. Hashimoto,et al.  PACAP is Implicated in the Stress Axes , 2011, Current pharmaceutical design.