Morphological diversity of single neurons in molecularly defined cell types
Author:
Peng HanchuanORCID, Xie Peng, Liu Lijuan, Kuang Xiuli, Wang YiminORCID, Qu LeiORCID, Gong HuiORCID, Jiang ShengdianORCID, Li AnanORCID, Ruan Zongcai, Ding Liya, Yao ZizhenORCID, Chen Chao, Chen Mengya, Daigle Tanya L., Dalley Rachel, Ding Zhangcan, Duan Yanjun, Feiner Aaron, He Ping, Hill Chris, Hirokawa Karla E., Hong Guodong, Huang Lei, Kebede SaraORCID, Kuo Hsien-Chi, Larsen Rachael, Lesnar Phil, Li Longfei, Li Qi, Li Xiangning, Li Yaoyao, Li Yuanyuan, Liu AnORCID, Lu Donghuan, Mok Stephanie, Ng Lydia, Nguyen Thuc Nghi, Ouyang Qiang, Pan Jintao, Shen Elise, Song Yuanyuan, Sunkin Susan M., Tasic BosiljkaORCID, Veldman Matthew B., Wakeman Wayne, Wan Wan, Wang Peng, Wang Quanxin, Wang Tao, Wang Yaping, Xiong Feng, Xiong Wei, Xu Wenjie, Ye Min, Yin Lulu, Yu Yang, Yuan Jia, Yuan JingORCID, Yun Zhixi, Zeng Shaoqun, Zhang Shichen, Zhao Sujun, Zhao Zijun, Zhou Zhi, Huang Z. JoshORCID, Esposito Luke, Hawrylycz Michael J.ORCID, Sorensen Staci A., Yang X. WilliamORCID, Zheng Yefeng, Gu ZhongzeORCID, Xie WeiORCID, Koch ChristofORCID, Luo Qingming, Harris Julie A., Wang Yun, Zeng HongkuiORCID
Abstract
AbstractDendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference71 articles.
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