Cellular anatomy of the mouse primary motor cortex

Muñoz-Castañeda, Rodrigo; Zingg, Brian; Matho, Katherine; Chen, Xiaoyin; Wang, Quanxin; Foster, Nicholas N.; Anan, Li; Narasimhan, Arun; Hirokawa, Karla E.; Huo, Bing-Xing; Bannerjee, Samik; Korobkova, Laura; Park, Chris Sin; Park, Young-Gyun; Bienkowski, Michael S.; Chon, Uree; Wheeler, Diek W.; Li, Xiangning; Wang, Yun; Naeemi, Maitham; Xie, Peng; Liu, Lijuan; Kelly, Kathleen; An, Xu; Attili, Sarojini M.; Bowman, Ian; Bludova, Anastasiia; Çetin, Ali; Ding, Liya; Drewes, Rhonda; D’Orazi, Florence D.; Elowsky, Corey; Fischer, Stephan; Galbavy, William; Gao, Lei; Gillis, Jesse; Groblewski, Peter A.; Gou, Lin; Hahn, Joel D.; Hatfield, Joshua; Hintiryan, Houri; Huang, Junxiang; Kondo, Hideki; Kuang, Xiuli; Lesnar, Philip; Li, Xu; Li, Yaoyao; Lin, Meng-Kuan; Lo, D.C.W.; Mizrachi, Judith; Mok, Stéphanie; Nicovich, Philip R.; Palaniswamy, Ramesh; Palmer, Jason; Qi, Xiaoli; Shen, Elise; Sun, Yuchi; Tao, Huizhong W.; Wakemen, Wayne; Wang, Yimin; Yao, Shenqin; Yuan, Jing; Zhan, Huiqing; Zhu, Muye; Ng, Lydia; Zhang, Li I.; Lim, Byung Kook; Hawrylycz, Michael; Gong, Hui; Gee, James C.; Kim, Yongsoo; Chung, Kwanghun; Yang, Xiangdong; Peng, Hanchuan; Luo, Qi; Mitra, Partha P.; Zador, Anthony M.; Zeng, Hongkui; Ascoli, Giorgio A.; Huang, Zirui; Osten, Pavel; Harris, Julie A.; Dong, Hong‐Wei

doi:10.1038/s41586-021-03970-w

Cited by 147 publications

(142 citation statements)

References 79 publications

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“…In these studies, we derive a cross-species consensus molecular taxonomy of cell types using scRNA-seq or single-nucleus RNA sequencing (snRNA-seq), DNA methylation and chromatin accessibility data [37][38][39][40] . In mouse, we map the spatial cellular organization by multiplexed error-robust fluorescence in situ hybridization (MERFISH) 41 , characterize morphological and electrophysiological properties by multimodal profiling using patch clamp recording, biocytin staining and scRNA-seq (Patch-seq) 42,43 , describe the cellular input-output wiring diagrams by anterograde and retrograde tracing 44 , identify glutamatergic neuron axon projection patterns by Epi-retro-seq 45 , Retro-MERFISH 41 and single-neuron complete morphology reconstruction 46 , and describe transgenic driver lines targeting glutamatergic cell types on the basis of marker genes and lineages 47 . Finally, we integrate this information into a cohesive description of cell types in MOp.…”

Section: Articlementioning

confidence: 99%

“…A comprehensive cellular resolution input-output MOp wiring diagram was generated by combining classic tracers, genetic viral labelling in Cre driver lines and single-neuron reconstructions with high-resolution, brain-wide imaging, precise 3D registration to CCF and computational analyses 44 .…”

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

“…We first systematically characterized the global inputs and outputs of MOp upper limb (MOp-ul) region using classic anterograde (Phaseolus vulgaris leucoagglutinin (PHAL)) and retrograde (cholera toxin b (CTb)) tract tracing 44 (Fig. 6a).…”

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

“…We generated a fine-grained areal and laminar distribution map of multiple MOp-ul projection neuron populations using retrograde tracing 44 (Extended Data Fig. 4a).…”

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

“…Viral tracers were used to systematically examine MOp-ul cell subclass-specific inputs and outputs 44 (Extended Data Fig. 4b).…”

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

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A multimodal cell census and atlas of the mammalian primary motor cortex

Callaway¹,

Dong²,

Ecker³

et al. 2021

Nature

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347

226

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Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

show abstract

Section: Articlementioning

confidence: 99%

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

“…We generated a fine-grained areal and laminar distribution map of multiple MOp-ul projection neuron populations using retrograde tracing 44 (Extended Data Fig. 4a).…”

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

“…Viral tracers were used to systematically examine MOp-ul cell subclass-specific inputs and outputs 44 (Extended Data Fig. 4b).…”

Section: Mop Input-output Wiring Diagrammentioning

confidence: 99%

See 3 more Smart Citations

A multimodal cell census and atlas of the mammalian primary motor cortex

Callaway¹,

Dong²,

Ecker³

et al. 2021

Nature

Self Cite

347

226

View full text Add to dashboard Cite

show abstract

Towards the Transcriptionally based Classification of L6b in the Adult Mouse Brain

Henning,

Bandiera,

Molnár

2023

Neocortical Neurogenesis in Development and Evolution

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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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Cellular anatomy of the mouse primary motor cortex

Cited by 147 publications

References 79 publications

A multimodal cell census and atlas of the mammalian primary motor cortex

A multimodal cell census and atlas of the mammalian primary motor cortex

Towards the Transcriptionally based Classification of L6b in the Adult Mouse Brain

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

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