The Allen Mouse Brain Common Coordinate Framework: A 3D Reference Atlas

Wang, Quanxin; Ding, Song‐Lin; Li, Yang; Royall, Josh; Feng, David; Lesnar, Phil; Graddis, Nile; Naeemi, Maitham; Facer, Benjamin A.C.; Ho, Anh; Dolbeare, Tim; Blanchard, Brandon; Dee, Nick; Wakeman, Wayne; Hirokawa, Karla E.; Szafer, Aaron; Sunkin, Susan M.; Oh, Seung Wook; Bernard, Amy; Phillips, John W.; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui; Harris, Julie A.; Ng, Lydia

doi:10.1016/j.cell.2020.04.007

Cited by 943 publications

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References 90 publications

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“…1a, Extended Data Figure 1, Supplementary Table 1, see Methods ) in 8-week-old male mice. Each dissection was made from 600 μm thick coronal brain slices according to the Allen Brain Reference Atlas (Extended Data Figure 1) 32 . For each region, snATAC-seq libraries from two independent biological replicates were generated with a protocol 31 that had been optimized for automation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The brain regions studied were dissected from 600 μm-thick coronal slices generated from 8-week-old mouse brains (top panel). A total of 45 regions were dissected according to the Allen Brain Reference Atlas 32 . Shown is the frontal view of slice 4 and the dissected brain regions (middle panel, alphabetically labeled).…”

Section: Resultsmentioning

confidence: 99%

“…Brains were extracted from 56-63 day old mice and sectioned into 600 μm coronal sections along the anterior-posterior axis in ice-cold dissection media. 14,15 Specific brain regions were dissected according to the Allen Brain Reference Atlas 32 (Extended Data Figure 1) and nuclei isolated as described. 15…”

Section: Methodsmentioning

confidence: 99%

“… a Schematic of brain sample dissection strategy. Mouse brains were cut into 600 μm thick coronal slices; b 45 regions were dissected from eleven coronal slices according to the Allen Brain Reference Atlas 32 . Shown is the frontal view of slice 1-11 and isolated regions.…”

Section: Extended Data Figurementioning

confidence: 99%

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An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

Preissl

Hou

et al. 2020

Preprint

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25The mammalian cerebrum performs high level sensory, motor control and cognitive 26 functions through highly specialized cortical networks and subcortical nuclei. Recent 27 surveys of mouse and human brains with single cell transcriptomics 1-3 and high-28 throughput imaging technologies 4,5 have uncovered hundreds of neuronal cell types and 29 a variety of non-neuronal cell types distributed in different brain regions, but the cell-type-30 specific transcriptional regulatory programs responsible for the unique identity and 31 function of each brain cell type have yet to be elucidated. Here, we probe the accessible 32 chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse 33 isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to 34 define 491,818 candidate cis regulatory DNA elements in 160 distinct sub-types. We link 35 a significant fraction of them to putative target genes expressed in diverse cerebral cell 36 types and uncover transcriptional regulators involved in a broad spectrum of molecular 37 and cellular pathways in different neuronal and glial cell populations. Our results provide 38 a foundation for comprehensive analysis of gene regulatory programs of the mammalian 39 brain and assist in the interpretation of non-coding risk variants associated with various 40 neurological disease and traits in humans. To facilitate the dissemination of information, 41 we have set up a web portal (http://catlas.org/mousebrain).42 45 functions such as sensory processing, motor control, emotion, and cognition 6 . It is divided 46 into two hemispheres, each consisting of the cerebral cortex and various cerebral nuclei. 47The cerebral cortex is further divided into isocortex and allocortex. Isocortex, 48 characterized by six cortical layers, is a phylogenetically more recent structure that has 49 further expanded greatly in primates. It is responsible for sensory motor integration, 50 decision making, volitional motor command and reasoning. The allocortex, by contrast, is 51 phylogenetically the older structure that features three or four cortical layers. It includes 52 the olfactory bulb responsible for processing the sense of smell and the hippocampus 53 involved in learning, memory and spatial navigation. 54 55 The cerebral cortex and basal ganglia are made up of a vast number of neurons and glial 56 cells. The neurons can be classified into different types of excitatory projection neurons 57 and inhibitory interneurons, defined by the neural transmitters they produce and their 58 connective patterns with other neurons 7-9 . Understanding how the identity and function of 59 each brain cell type is established during development and modified by experience is one 60 of the fundamental challenges in brain research. Recent single cell RNA-seq and high 61 throughput imaging experiments have produced detailed cell atlases for both mouse and 62human brains 3-5,10-15 , leading to a comprehensive view of gene expression patterns in 63 different brain regions, c...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Extended Data Figurementioning

confidence: 99%

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An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

Preissl

Hou

et al. 2020

Preprint

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“…We then performed MERFISH measurements on a series of coronal slices of the adult mouse brain (Bregma +2.4 to -0.6) at 100 µm intervals along the anterior-posterior axis and imaged the MOp region selected according to the Allen Mouse Common Coordinate Framework version 3 (CCF v3) 41 (Figure 1a). Individual RNA molecules were clearly detected and identified in the tissue slices (Extended Data Figure 1a).…”

Section: Single-cell Gene Expression Profiling and Cell Type Identifimentioning

confidence: 99%

Molecular, spatial and projection diversity of neurons in primary motor cortex revealed by in situ single-cell transcriptomics

Zhang

Eichhorn

Zingg

et al. 2020

Preprint

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A mammalian brain is comprised of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing provides a powerful approach to identify cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain 1-3 . Single-cell epigenomic profiling 4,5 further provides information on gene-regulatory signatures of different cell types. Understanding how different cell types contribute to brain function, however, requires knowledge of their spatial organization and connectivity, which is not preserved in sequencing-based methods that involve cell dissociation 3,6 . Here, we used an in situ single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH) 7 , to generate a molecularly defined and spatially resolved cell atlas of the mouse primary motor cortex (MOp). We profiled

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Mapping the Function of Whole‐Brain Projection at the Single Neuron Level

Zhou

et al. 2022

Advanced Science

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Axonal projection conveys neural information. The divergent and diverse projections of individual neurons imply the complexity of information flow. It is necessary to investigate the relationship between the projection and functional information at the single neuron level for understanding the rules of neural circuit assembly, but a gap remains due to a lack of methods to map the function to whole‐brain projection. Here an approach is developed to bridge two‐photon calcium imaging in vivo with high‐resolution whole‐brain imaging based on sparse labeling with the genetically encoded calcium indicator GCaMP6. Reliable whole‐brain projections are captured by the high‐definition fluorescent micro‐optical sectioning tomography (HD‐fMOST). A cross‐modality cell matching is performed and the functional annotation of whole‐brain projection at the single‐neuron level (FAWPS) is obtained. Applying it to the layer 2/3 (L2/3) neurons in mouse visual cortex, the relationship is investigated between functional preferences and axonal projection features. The functional preference of projection motifs and the correlation between axonal length in MOs and neuronal orientation selectivity, suggest that projection motif‐defined neurons form a functionally specific information flow, and the projection strength in specific targets relates to the information clarity. This pipeline provides a new way to understand the principle of neuronal information transmission.

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The Allen Mouse Brain Common Coordinate Framework: A 3D Reference Atlas

Abstract: Highlights d Created a 3D average template brain from 1,675 mice at 10mm voxel resolution d Delineated 43 isocortical areas from multiple surface views using curved coordinates d Delineated 329 subcortical areas, 8 ventricle structures, and 81 fiber tracts in 3D

Cited by 943 publications

References 90 publications

An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

Molecular, spatial and projection diversity of neurons in primary motor cortex revealed by in situ single-cell transcriptomics

Mapping the Function of Whole‐Brain Projection at the Single Neuron Level

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