A Cell Atlas for the Mouse Brain

Despite vast numbers of studies of stained cells in the mouse brain, no current brain atlas provides region-by-region neuron counts. In fact, neuron numbers are only available for about 4% of brain of regions and estimates often vary by as much as 3-fold. Here we provide a first 3D cell atlas for the whole mouse brain, showing cell positions constructed algorithmically from whole brain Nissl and gene expression stains, and compared against values from the literature. The atlas provides the densities and positions of all excitatory and inhibitory neurons, astrocytes, oligodendrocytes, and microglia in each of the 737 brain regions defined in the AMBA. The atlas is dynamic, allowing comparison with previously reported numbers, addition of cell types, and improvement of estimates as new data is integrated. The atlas also provides insights into cellular organization only possible at this whole brain scale, and is publicly available.

[1]  Henry Markram,et al.  Cell Densities in the Mouse Brain: A Systematic Review , 2018, Front. Neuroanat..

[2]  Milos Pekny,et al.  Versatile and Simple Approach to Determine Astrocyte Territories in Mouse Neocortex and Hippocampus , 2013, PloS one.

[3]  Melitta Schachner,et al.  Age‐dependent loss of parvalbumin‐expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene , 2015, Journal of neurochemistry.

[4]  N. Baumann,et al.  Determination of glial fibrillary acidic protein (GFAP) in human brain tumors , 1978, Journal of the Neurological Sciences.

[5]  J. Price.  :Allen Reference Atlas: A Digital Color Brain Atlas of the C57BL/6J Male Mouse , 2008 .

[6]  J. Tepper,et al.  Heterogeneity and Diversity of Striatal GABAergic Interneurons , 2010, Front. Neuroanat..

[7]  J. Vega,et al.  Reduction of glial fibrillary acidic protein-immunoreactive astrocytes in some brain areas of old hairless rhino-j mice (hr-rh-j) , 2001, Neuroscience Letters.

[8]  S. Linnarsson,et al.  Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq , 2015, Science.

[9]  J Tanaka,et al.  [MBP and GFAP immunohistochemistry of oligodendrogliomas with relationship to myelin-forming glia in cell differentiation]. , 1986, No to shinkei = Brain and nerve.

[10]  Mohamed Doulazmi,et al.  QUANTITATIVE ANALYSIS OF MICROGLIAL CELLS IN THE DEGENERATING CEREBELLUM OF THE STAGGERER (RORAsg/sg) MUTANT MOUSE , 2005, Journal of neurogenetics.

[11]  Yuko Saito,et al.  TMEM119 marks a subset of microglia in the human brain , 2016, Neuropathology : official journal of the Japanese Society of Neuropathology.

[12]  Jon H. Kaas,et al.  Updated Neuronal Scaling Rules for the Brains of Glires (Rodents/Lagomorphs) , 2011, Brain, Behavior and Evolution.

[13]  Miao He,et al.  Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism , 2017, Cell.

[14]  V. Perry,et al.  Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain , 1990, Neuroscience.

[15]  Junhua Xiao,et al.  Gas6 Increases Myelination by Oligodendrocytes and Its Deficiency Delays Recovery following Cuprizone-Induced Demyelination , 2011, PloS one.

[16]  Erwan Bezard,et al.  Astrocytosis in parkinsonism: considering tripartite striatal synapses in physiopathology? , 2014, Front. Aging Neurosci..

[17]  S. Herculano‐Houzel,et al.  Cellular scaling rules for rodent brains , 2006, Proceedings of the National Academy of Sciences.

[18]  Y. Xing,et al.  A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function , 2008, The Journal of Neuroscience.

[19]  Cornelius Gross,et al.  Firing Properties of Genetically Identified Dorsal Raphe Serotonergic Neurons in Brain Slices , 2016, Front. Cell. Neurosci..

[20]  Emery N. Brown,et al.  The BRAIN Initiative: developing technology to catalyse neuroscience discovery , 2015, Philosophical Transactions of the Royal Society B: Biological Sciences.

[21]  A. Steen,et al.  Quantitative Morphological Analyses of the Striatum and Cerebellum of Tenascin-R deficient mice , 2006 .

[22]  Janina Alexandra Förster,et al.  Quantitative morphological analysis of the neostriatum and the cerebellum of tenascin-C deficient mice , 2008 .

[23]  Peter E. Braun,et al.  Overexpression of 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase in Transgenic Mice Alters Oligodendrocyte Development and Produces Aberrant Myelination , 1996, Molecular and Cellular Neuroscience.

[24]  James G. King,et al.  Reconstruction and Simulation of Neocortical Microcircuitry , 2015, Cell.

[25]  Hiroshi Sekiya,et al.  A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing , 2018, Nature Neuroscience.

[26]  Karlheinz Meier,et al.  Introducing the Human Brain Project , 2011, FET.

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

[28]  V. Gallo,et al.  Spatial and temporal expression of S100B in cells of oligodendrocyte lineage , 2005, Glia.

[29]  J. Bolam,et al.  Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat , 2008, Neuroscience.

[30]  Charles Watson,et al.  Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones , 2013, Front. Neuroanat..

[31]  Melitta Schachner,et al.  Heterozygosity for the mutated X-chromosome-linked L1 cell adhesion molecule gene leads to increased numbers of neurons and enhanced metabolism in the forebrain of female carrier mice , 2012, Brain Structure and Function.

[32]  Roberto Lent,et al.  Isotropic Fractionator: A Simple, Rapid Method for the Quantification of Total Cell and Neuron Numbers in the Brain , 2005, The Journal of Neuroscience.

[33]  F. Helmchen,et al.  Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo , 2005, Science.

[34]  Robert W. Williams,et al.  Increased brain size and glial cell number in CD81‐null mice , 2002, The Journal of comparative neurology.

[35]  H. Markram.  The Blue Brain Project , 2006, Nature Reviews Neuroscience.

[36]  H. Goto,et al.  Microvessel and astroglial cell densities in the mouse hippocampus. , 1992, Journal of anatomy.