An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input–output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.
|Number of pages||8|
|Publication status||Published - 2021 Oct 7|
Bibliographical noteFunding Information:
Acknowledgements B.Z., H.H., H.-W.D., I.B., L. Gao, L. Gou, L.K., M.S.B., M.Z. and N.N.F. thank K. Cotter, L. Gacia, D. Lo, T. Boesen, C. Cao, M. Becerra, M. Fayzullina and C. Mun for their technical and informatics support. Their work was supported by NIH U01MH114829 (to H.-W.D., G.A.A. and B.K.L.), R01MH094360 (H.-W.D.), U19MH114821 (Z.J.H. and P. Arlotta) and U19MH114831 (J. Ecker/E. Callaway). D.W.W., S.M.A. and G.A.A. gratefully acknowledge the assistance of T. Ferreira in accessing the API for batch downloading the Janelia MouseLight neuron dataset and for providing constructive feedback on the corresponding analysis. Their work was supported by NIH U01MH114829 (to H.-W.D., G.A.A. and B.K.L.), R01NS39600 (to G.A.A.), and R01NS86082 (to G.A.A. and D. Cox). A.C., F.D., H. Zeng, J.A.H., K.E.H., M.N., M.H., P.A.G., P.L., P.R.N., Q.W., S.Y., W.W., and Yun Wang. are grateful to the Transgenic Colony Management, Neurosurgery and Behavior, Lab Animal Services, Molecular Genetics, Imaging, and Histology teams at the Allen Institute for technical support. In particular, they thank V. Wright, M. McGraw, L. Potekhina, L. Kuan and A. Williford from these teams. Their work was supported by the Allen Institute for Brain Science and by NIH grants R01EY023173, U01MH105982 and U19MH114830 to H. Zeng. The authors thank the Allen Institute founder, P. G. Allen, for his vision, encouragement, and support. Y.-C.S., A.M.Z. and X.C. acknowledge members of the MAPseq core facility, including H. Zhan and Y. Li, for facilitating BARseq data production, and W. Wadolowski for technical support. Their work was supported by NIH 5R01NS073129, 5R01DA036913, RF1MH114132, and U01MH109113 to A.M.Z., R01MH113005 and R01LM012736 to J.G., and U19MH114821 to A.M.Z. and J.G.; the Brain Research Foundation (BRF-SIA-2014-03 to A.M.Z.), IARPA MICrONS (D16PC0008 to A.M.Z.), Paul Allen Distinguished Investigator Award (to A.M.Z.), Simons Foundation (350789 to X.C.), Chan Zuckerberg Initiative (2017-0530 ZADOR/ALLEN INST(SVCF) SUB to A.M.Z.), and R. Lourie (to A.M.Z.). Their work was additionally supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the FY18 PRMRP Discovery Award Program W81XWH1910083 to X.C. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. In conducting research using animals, the investigator adheres to the laws of the United States and regulations of the Department of Agriculture. B.Z., J.H., H.W.T. and L.I.Z. were also supported by NIH R01DC008983, RF1MH114112, U01MH116990, and EY019049. J.G. was supported by NIH R01NS096720. J.T.H., K.K., K.S.M., W.G., X.A. and Z.J.H. were supported in part by NIH 5U19MH114821-03 to Z.J.H. P.P.M. was supported by NIH EB022899, MH114824, MH114821, and NS107466, the Mather Foundation, and a Crick-Clay Professorship. X.W.Y. and H.-W.D. were supported by NIH BRAIN Initiative MH106008; X.W.Y., H.-W.D., M.Z. and N.N.F. were supported by NIH BRAIN Initiative MH117079. Y.K. was supported by NIH R01MH116176 and NIH RF1MH12460501. H.P., L.L., P.X., L.D. and Yimin Wang were supported by an Open Science initiative at Southeast University. A.L, Xiangning Li, H.G. and Q.L. were supported by NNSFC 61890953 and 61890954 Author contributions Co-corresponding authors: H.-W.D., J.A.H., P.O., Z.J.H. and G.A.A. conceived the project, supervised data generation, conducted data analysis, constructed figures and wrote the manuscript. Co-first authors: R.M.-C., B.Z., K.S.M., X.C. and Q.W. conducted data collection and data analysis, constructed figures and extended data figures, and participated in writing the manuscript. Other co-authors who made significant contributions to data generation, generating extended data figures and Supplementary Information, developing computational tools, as well as project management: N.N.F., A.L., A.N., K.E.H., B.H., S.B., L.K., C.S.P., Y.-G.P., M.S.B., U.C., D.W.W., X.L., Yun Wang, M.N., P.X., L.L. and K.K. Other co-authors who participated in data generations and analysis, developing computational tools, figure generation, morphological reconstructions, as well as manuscript editing (these authors are listed in an alphabetic order): X.A., S.M.A., I.B., A.B., A.C., L.D., R.D., F.D., C.E., S.F., W.G., L. Gao, J.G., P.A.G., L. Gou, J.D.H., J.T.H., H.H., J.J.H., H.K., X.K., P.L., X.L., Y.L., M.L., D.L., J.M., S.M., P.R.N., R.P., J.P., X.Q., E.S., Y.-C.S., H.W.T., W.W., Yimin Wang, S.Y., J.Y., M.Z. and L.N. Other BICCN contributing principal investigators: H. Zeng, A.M.Z., P.P.M., Q.L., H.P., X.W.Y., K.C., Y.K., J.C.G., H.G., M.H., B.K.L. and L.I.Z.
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