Cellular Anatomy of the Mouse Primary Motor Cortex

Rodrigo Muñoz-Castañeda, Brian Zingg, Katherine S. Matho, Quanxin Wang, Xiaoyin Chen, Nicholas N. Foster, Arun Narasimhan, Anan Li, Karla E. Hirokawa, Bingxing Huo, Samik Bannerjee, Laura Korobkova, Chris Sin Park, Young-Gyun Park, Michael S. Bienkowski, Uree Chon, Diek W. Wheeler, Xiangning Li, Yun Wang, Kathleen Kelly, Xu An, Sarojini M. Attili, Ian Bowman, Anastasiia Bludova, Ali Cetin, Liya Ding, Rhonda Drewes, Florence D’Orazi, Corey Elowsky, Stephan Fischer, William Galbavy, Lei Gao, Jesse Gillis, Peter A. Groblewski, Lin Gou, Joel D. Hahn, Joshua T. Hatfield, Houri Hintiryan, Jason Huang, Hideki Kondo, Xiuli Kuang, Philip Lesnar, Xu Li, eYaoyao Li, Mengkuan Lin, Lijuan Liu, Darrick Lo, V Judith Mizrachi, Stephanie Mok, Maitham Naeemi, Philip R. Nicovich, Ramesh Palaniswamy, Jason Palmer, Xiaoli Qi, Elise Shen, Yu-Chi Sun, Huizhong Tao, Wayne Wakemen, Yimin Wang, Peng Xie, Shenqin Yao, Jin Yuan, Muye Zhu, Lydia Ng, Li I. Zhang, Byung Kook Lim, Michael Hawrylycz, Hui Gong, James C. Gee, Yongsoo Kim, V Hanchuan Peng, Kwanghun Chuang, X William Yang, Qingming Luo, Partha P. Mitra, Anthony M. Zador, Hongkui Zeng, Giorgio A. Ascoli, Z Josh Huang, Pavel Osten, Julie A. Harris, Hong-Wei Dong

Resources for "Cellular Anatomy of the Mouse Primary Motor Cortex", 2021

Abstract

An essential step toward understanding brain function is to establish a cellular-resolution structural framework upon which multi-scale and multi-modal information spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, through a collaborative effort from the Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based description of one brain structure - the primary motor cortex upper limb area (MOp-ul) of the mouse. Applying state-of-the-art labeling, imaging, computational, and neuroinformatics tools, we delineated the MOp-ul within the Mouse Brain 3D Common Coordinate Framework (CCF). We defined over two dozen MOp-ul projection neuron (PN) types by their anterograde targets; the spatial distribution of their somata defines 11 cortical sublayers, a significant refinement of the classic notion of cortical laminar organization. We further combine multiple complementary tracing methods (classic tract tracing, cell type-based anterograde, retrograde, and transsynaptic viral tracing, high-throughput BARseq, and complete single cell reconstruction) to systematically chart cell type-based MOp input-output streams. As PNs link distant brain regions at synapses as well as host cellular gene expression, our construction of a PN type resolution MOp-ul wiring diagram will facilitate an integrated analysis of motor control circuitry across the molecular, cellular, and systems levels. This work further provides a roadmap towards a cellular resolution description of mammalian brain architecture.

Main Figures

Extended Data Figure 1. Overview of methods, analyses and resources used and generated by the BICCN anatomy group.
Figure 1. Anatomical delineation of the MOp upper limb (MOp-ul) and its organization.
Figure 2. Brain-wide MOp-ul projection patterns by layer and class.
Figure 3. Brain-wide inputs to MOp-ul by layer and class.
Figure 4. Projection mapping with single cell resolution using BARseq.
Figure 5. Full morphological reconstruction reveals diverse single cell projection motifs.
Extended Data Figures

Key Resources

The Mouse Connectome Project (MCP) seeks to develop a multimodal multiscale connectome and cell-type map of the mammalian brain using advanced tracing, imaging, and computational methods. MCP seeks to develop a multimodal multiscale connectome and cell-type map of the mammalian brain using advanced tracing, imaging, and computational methods.

iConnectome

The Brain Architecture Project is a collaborative effort aimed at creating an integrated resource containing knowledge about nervous system architecture in multiple species, with extensive whole-brain light microscopic data sets available for Mouse and Marmoset as well as for other species including Zebra Finch and Human.

Brain Archictecture Project

NeuroMorpho.Org is a centrally curated inventory of digitally reconstructed neurons associated with peer-reviewed publications. It contains contributions from over 500 laboratories worldwide and is continuously updated as new morphological reconstructions are collected, published, and shared. To date, NeuroMorpho.Org is the largest collection of publicly accessible 3D neuronal reconstructions and associated metadata.

Neuromorpho.org

The Allen Institute for Brain Science has completed the three-dimensional mapping of the mouse cortex as part of the Allen Mouse Common Coordinate Framework (CCF): a standardized spatial coordinate system for comparing many types of data on the brain from the suite of Allen Brain Atlas resources. The Common Coordinate Framework was built by carefully averaging the anatomy of 1,675 specimens from the Allen Mouse Brain Connectivity Atlas. Researchers used transgenic mouse lines and data from viral tracers to draw boundaries between 43 regions of the cortex. The end result is a template brain rendered in three dimensions, which serves as a useful guide to mouse brain anatomy as well as a platform for comparing data across many Allen Brain Atlas resources

Allen Reference Atlas and Franklin-Paxinos Atlas