Brain-wide single neuron reconstruction reveals morphological diversity in molecularly defined striatal, thalamic, cortical and claustral neuron types

Autor: Susan M. Sunkin, Zizhen Yao, Qi Li, Tanya L. Daigle, Yun Wang, Michael Hawrylycz, Jia Yuan, Donghuan Lu, Bosiljka Tasic, Lulu Yin, Yuanyuan Song, Z. Josh Huang, Karla E. Hirokawa, Zheng Yefeng, Matthew B. Veldman, Lei Huang, Luke Esposito, Feng Xiong, Shaoqun Zeng, An Liu, Liya Ding, Guodong Hong, Jintao Pan, Yaoyao Li, Wei Xiong, Qiang Ouyang, Yang Yu, Thuc Nghi Nguyen, Qingming Luo, Yimin Wang, Xiangning Li, Mengya Chen, Tao Wang, Zhangcan Ding, Lei Qu, Lydia Ng, Min Ye, Hsien-Chi Kuo, Peng Xie, Yuanyuan Li, Rachael Larsen, Zhixi Yun, Chris Hill, Julie A. Harris, Peng Wang, Longfei Li, Elise Shen, Lijuan Liu, Wan Wan, Sujun Zhao, Hui Gong, Zhongze Gu, Zongcai Ruan, Jing Yuan, Christof Koch, Xiangdong Yang, Wenjie Xu, Hongkui Zeng, Aaron Feiner, Stephanie Mok, Yanjun Duan, Shichen Zhang, Chao Chen, Yaping Wang, Wayne Wakeman, Phil Lesnar, Sara Kebede, Ping He, Staci A. Sorensen, Zijun Zhao, Anan Li, Hanchuan Peng, Xiuli Kuang, Shengdian Jiang, Zhi Zhou, Quanxin Wang, Wei Xie
Rok vydání: 2020
Předmět:
Popis: Ever since the seminal findings of Ramon y Cajal, dendritic and axonal morphology has been recognized as a defining feature of neuronal types. Yet our knowledge concerning the diversity of neuronal morphologies, in particular distal axonal projection patterns, is extremely limited. To systematically obtain single neuron full morphology on a brain-wide scale, we established a platform with five major components: sparse labeling, whole-brain imaging, reconstruction, registration, and classification. We achieved sparse, robust and consistent fluorescent labeling of a wide range of neuronal types by combining transgenic or viral Cre delivery with novel transgenic reporter lines. We acquired high-resolution whole-brain fluorescent images from a large set of sparsely labeled brains using fluorescence micro-optical sectioning tomography (fMOST). We developed a set of software tools for efficient large-volume image data processing, registration to the Allen Mouse Brain Common Coordinate Framework (CCF), and computer-assisted morphological reconstruction. We reconstructed and analyzed the complete morphologies of 1,708 neurons from the striatum, thalamus, cortex and claustrum. Finally, we classified these cells into multiple morphological and projection types and identified a set of region-specific organizational rules of long-range axonal projections at the single cell level. Specifically, different neuron types from different regions follow highly distinct rules in convergent or divergent projection, feedforward or feedback axon termination patterns, and between-cell homogeneity or heterogeneity. Major molecularly defined classes or types of neurons have correspondingly distinct morphological and projection patterns, however, we also identify further remarkably extensive morphological and projection diversity at more fine-grained levels within the major types that cannot presently be accounted for by preexisting transcriptomic subtypes. These insights reinforce the importance of full morphological characterization of brain cell types and suggest a plethora of ways different cell types and individual neurons may contribute to the function of their respective circuits.
Databáze: OpenAIRE