美国波士顿儿童医院Zhigang He和美国艾伦脑科学研究所Hongkui Zeng等共同合作，近期取得重要工作进展，他们研究开发出了小鼠全脑脊髓投射神经元的转录组分类学。相关研究成果2023年12月13日在线发表于《自然》杂志上。

据介绍，大脑通过脊髓投射神经元（SPN）控制几乎所有的身体功能，这些神经元将命令信号从大脑传递到脊髓。然而，全脑SPN的全面分子表征仍然缺乏。

研究人员对总共65002个SPN进行了转录组分析，确定了76种区域特异性SPN类型，并将这些类型映射到整个小鼠大脑的伴随图谱中。该分类揭示了SPN的三个组成部分：（1）来自皮层、红核和小脑的分子同质兴奋性SPN，具有适合点对点通信的体位脊髓终端；（2） 网状结构中的异质群体，具有广泛的脊髓终止模式，适合于传递与整个脊髓活动相关的命令；以及（3）在下丘脑、中脑和网状结构中表达慢效神经递质或神经肽的调节神经元，用于脑脊髓信号的“增益设置”。

此外，该图谱揭示了一种LIM同源盒转录因子编码，该编码将网状螺旋体神经元分为五个分子不同且空间分离的群体。最后，研究人员发现了一个较大SPN亚群的转录特征，并将其与快速放电电生理特性相关联。

总之，这项研究建立了全脑SPN的全面分类，并深入了解了SPN在介导大脑对身体功能的控制中的功能组织。

附：英文原文

Title: A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons

Author: Winter, Carla C., Jacobi, Anne, Su, Junfeng, Chung, Leeyup, van Velthoven, Cindy T. J., Yao, Zizhen, Lee, Changkyu, Zhang, Zicong, Yu, Shuguang, Gao, Kun, Duque Salazar, Geraldine, Kegeles, Evgenii, Zhang, Yu, Tomihiro, Makenzie C., Zhang, Yiming, Yang, Zhiyun, Zhu, Junjie, Tang, Jing, Song, Xuan, Donahue, Ryan J., Wang, Qing, McMillen, Delissa, Kunst, Michael, Wang, Ning, Smith, Kimberly A., Romero, Gabriel E., Frank, Michelle M., Krol, Alexandra, Kawaguchi, Riki, Geschwind, Daniel H., Feng, Guoping, Goodrich, Lisa V., Liu, Yuanyuan, Tasic, Bosiljka, Zeng, Hongkui, He, Zhigang

Issue&Volume: 2023-12-13

Abstract: The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for ‘gain setting’ of brain–spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

DOI: 10.1038/s41586-023-06817-8

Source: https://www.nature.com/articles/s41586-023-06817-8