An interactive framework for whole-brain maps at cellular resolution

To deconstruct the architecture and function of brain circuits, it is necessary to generate maps of neuronal connectivity and activity on a whole-brain scale. New methods now enable large-scale mapping of the mouse brain at cellular and subcellular resolution. We developed a framework to automatically annotate, analyze, visualize and easily share whole-brain data at cellular resolution, based on a scale-invariant, interactive mouse brain atlas. This framework enables connectivity and mapping projects in individual laboratories and across imaging platforms, as well as multiplexed quantitative information on the molecular identity of single neurons. As a proof of concept, we generated a comparative connectivity map of five major neuron types in the corticostriatal circuit, as well as an activity-based map to identify hubs mediating the behavioral effects of cocaine. Thus, this computational framework provides the necessary tools to generate brain maps that integrate data from connectivity, neuron identity and function.The authors present a new computational approach to automatically annotate, analyze, visualize and easily share whole-brain datasets at cellular resolution, based on a scale-invariant and interactive mouse brain reference atlas. The authors applied this framework to define the organization and cocaine-induced activity of corticostriatal circuits.

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

[2]  Sachie K. Ogawa,et al.  Whole-Brain Mapping of Direct Inputs to Midbrain Dopamine Neurons , 2012, Neuron.

[3]  Dai Feng,et al.  Computing and Displaying Isosurfaces in R , 2008 .

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

[5]  Fred L. Bookstein,et al.  Principal Warps: Thin-Plate Splines and the Decomposition of Deformations , 1989, IEEE Trans. Pattern Anal. Mach. Intell..

[6]  Patrik L. Ståhl,et al.  Visualization and analysis of gene expression in tissue sections by spatial transcriptomics , 2016, Science.

[7]  Justus M. Kebschull,et al.  High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA , 2016, Neuron.

[8]  Takashi Kawashima,et al.  Mapping brain activity at scale with cluster computing , 2014, Nature Methods.

[9]  Tianyi Mao,et al.  A comprehensive thalamocortical projection map at the mesoscopic level , 2014, Nature Neuroscience.

[10]  George M. Church,et al.  Highly Multiplexed Subcellular RNA Sequencing in Situ , 2014, Science.

[11]  Ola Söderberg,et al.  In situ detection and genotyping of individual mRNA molecules , 2010, Nature Methods.

[12]  Feng Li,et al.  The complete connectome of a learning and memory centre in an insect brain , 2017, Nature.

[13]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[14]  Kevin L. Briggman,et al.  Structural neurobiology: missing link to a mechanistic understanding of neural computation , 2012, Nature Reviews Neuroscience.

[15]  Dirk Eddelbuettel,et al.  Rcpp: Seamless R and C++ Integration , 2011 .

[16]  Richard Kronland-Martinet,et al.  A real-time algorithm for signal analysis with the help of the wavelet transform , 1989 .

[17]  Ling Fu,et al.  Whole-Brain Mapping of Inputs to Projection Neurons and Cholinergic Interneurons in the Dorsal Striatum , 2015, PloS one.

[18]  Keiichi Abe,et al.  Topological structural analysis of digitized binary images by border following , 1985, Comput. Vis. Graph. Image Process..

[19]  T. Curran,et al.  Expression of c-fos protein in brain: metabolic mapping at the cellular level. , 1988, Science.

[20]  A. Graybiel,et al.  Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Mao-Jiun J. Wang,et al.  Image thresholding by minimizing the measures of fuzzines , 1995, Pattern Recognit..

[22]  Douglas B. Ehlenberger,et al.  Automated Three-Dimensional Detection and Shape Classification of Dendritic Spines from Fluorescence Microscopy Images , 2008, PloS one.

[23]  Anatol C. Kreitzer,et al.  Differential Innervation of Direct- and Indirect-Pathway Striatal Projection Neurons , 2013, Neuron.

[24]  Ghassan Hamarneh,et al.  Contour Correspondence via Ant Colony Optimization , 2007 .

[25]  Fabrice Mériaudeau,et al.  A Thin-Plate Spline Based Multimodal Prostate Registration with Optimal Correspondences , 2010, 2010 Sixth International Conference on Signal-Image Technology and Internet Based Systems.

[26]  C. Chiamulera,et al.  Common Neural Substrates for the Addictive Properties of Nicotine and Cocaine , 1997, Science.

[27]  Arthur W. Toga,et al.  Neural Networks of the Mouse Neocortex , 2014, Cell.

[28]  Michael I. Jordan,et al.  Hierarchical Mixtures of Experts and the EM Algorithm , 1994, Neural Computation.

[29]  Drew N. Robson,et al.  Brain-wide neuronal dynamics during motor adaptation in zebrafish , 2012, Nature.

[30]  Jiqiang Guo,et al.  Stan: A Probabilistic Programming Language. , 2017, Journal of statistical software.

[31]  Ian R. Wickersham,et al.  Monosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted Neurons , 2007, Neuron.

[32]  James A. Gagnon,et al.  Whole-organism lineage tracing by combinatorial and cumulative genome editing , 2016, Science.

[33]  Jeremy D. Schmahmann,et al.  A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale , 2009, PLoS Comput. Biol..

[34]  T. Crombleholme,et al.  Optimized large-scale production of high titer lentivirus vector pseudotypes. , 2004, Journal of virological methods.

[35]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[36]  Hang Zhou,et al.  NeuroGPS-Tree: automatic reconstruction of large-scale neuronal populations with dense neurites , 2015, Nature Methods.

[37]  Eric T. Trautman,et al.  A complete electron microscopy volume of the brain of adult Drosophila melanogaster , 2017 .

[38]  Ching Y. Suen,et al.  A fast parallel algorithm for thinning digital patterns , 1984, CACM.

[39]  Michael Broxton,et al.  SPED Light Sheet Microscopy: Fast Mapping of Biological System Structure and Function , 2015, Cell.

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

[41]  Charles R. Gerfen,et al.  Targeting Cre Recombinase to Specific Neuron Populations with Bacterial Artificial Chromosome Constructs , 2007, The Journal of Neuroscience.

[42]  Karl J. Friston,et al.  Statistical parametric mapping , 2013 .

[43]  Ian R. Wickersham,et al.  Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons , 2010, Nature Protocols.

[44]  Ulrich Bodenhofer,et al.  APCluster: an R package for affinity propagation clustering , 2011, Bioinform..

[45]  G. Silberberg,et al.  A Whole-Brain Atlas of Inputs to Serotonergic Neurons of the Dorsal and Median Raphe Nuclei , 2014, Neuron.

[46]  Kristopher J Preacher,et al.  Effect size measures for mediation models: quantitative strategies for communicating indirect effects. , 2011, Psychological methods.

[47]  Nico Stuurman,et al.  Computer Control of Microscopes Using µManager , 2010, Current protocols in molecular biology.

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

[49]  Nicholas N. Foster,et al.  The mouse cortico-striatal projectome , 2016, Nature Neuroscience.

[50]  F. N. van de Vosse,et al.  Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy , 2011, Biomechanics and Modeling in Mechanobiology.

[51]  R. W. Draft,et al.  Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system , 2007, Nature.

[52]  R. Yuste,et al.  The Brain Activity Map Project and the Challenge of Functional Connectomics , 2012, Neuron.

[53]  Avishek Adhikari,et al.  Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences , 2016, Cell.

[54]  M. Helmstaedter.  Cellular-resolution connectomics: challenges of dense neural circuit reconstruction , 2013, Nature Methods.

[55]  Allan R. Jones,et al.  An anatomic gene expression atlas of the adult mouse brain , 2009, Nature Neuroscience.

[56]  Douglas B. Ehlenberger,et al.  New techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales , 2005, Neuroscience.

[57]  Sl Harris.  Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartment and limbic subdivisions of the striatum , 1990 .

[58]  A. Graybiel.  The Basal Ganglia and Chunking of Action Repertoires , 1998, Neurobiology of Learning and Memory.

[59]  Partha P. Mitra,et al.  The Circuit Architecture of Whole Brains at the Mesoscopic Scale , 2014, Neuron.

[60]  G. Allan Johnson,et al.  Waxholm Space: An image-based reference for coordinating mouse brain research , 2010, NeuroImage.

[61]  A. Rose,et al.  Vision: human and electronic , 1973 .

[62]  Arrate Muñoz-Barrutia,et al.  3D reconstruction of histological sections: Application to mammary gland tissue , 2010, Microscopy research and technique.

[63]  Chia-Ling Tsai,et al.  A Broadly Applicable 3-D Neuron Tracing Method Based on Open-Curve Snake , 2011, Neuroinformatics.

[64]  Steven G. Johnson,et al.  The Design and Implementation of FFTW3 , 2005, Proceedings of the IEEE.

[65]  Stéphane Mallat,et al.  A Theory for Multiresolution Signal Decomposition: The Wavelet Representation , 1989, IEEE Trans. Pattern Anal. Mach. Intell..

[66]  Paul Murrell,et al.  Importing Vector Graphics: The grImport Package for R , 2009 .

[67]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

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

[69]  Z. Popovic.  Rethinking Algorithms for Games: Towards High-Fidelity Effects in Interactive Environments , 2007 .