基于项目组的雄性小鼠下丘脑肽能神经元表征，这一成果由中国科学院脑科学与智能技术卓越创新中心许晓鸿课题组经过不懈努力而取得。该项研究成果发表在2025年3月26日出版的《自然—神经科学》上。

在这里，该研究团队绘制了7000多个表达不同神经肽的雄性小鼠下丘脑神经元的全脑投影，确定了2大类和31种类型，并进行了单神经元投影组分析。这些类别/类型表现出区域偏倚的体细胞分布和特定的神经肽富集。值得注意的是，许多项目组类型将远程轴突支线扩展到不同的大脑区域，允许单个轴突共同调节多个目标。该团队在Orexin， Agrp和Pomc群体中发现了特定目标上某些肽能轴突的地形组织，以及不同的单神经元项目组模式。

此外，下丘脑肽能神经元在导水管周围灰质的亚域显示出相关的神经支配，并在下丘脑内组织成模块化的亚网络，为协调输出提供了结构基础。该数据集突出了下丘脑轴突投射的复杂性，为下丘脑功能背后的电路机制的未来研究奠定了基础。

据悉，下丘脑协调调节生理稳态和先天行为，但下丘脑轴突的详细排列尚不清楚。

附：英文原文

Title: Projectome-based characterization of hypothalamic peptidergic neurons in male mice

Author: Jiao, Zhuolei, Gao, Taosha, Wang, Xiaofei, Wang, Ao, Ma, Yawen, Feng, Li, Gao, Le, Gou, Lingfeng, Zhang, Wen, Biglari, Nasim, Boxer, Emma E., Steuernagel, Lukas, Ding, Xiaojing, Yu, Zixian, Li, Mingjuan, Gao, Mengtong, Hao, Mingkun, Zhou, Hua, Cao, Xuanzi, Li, Shuaishuai, Jiang, Tao, Qi, Jiamei, Jia, Xueyan, Feng, Zhao, Ren, Biyu, Chen, Yu, Shi, Xiaoxue, Wang, Dan, Wang, Xinran, Han, Luyao, Liang, Yikai, Qian, Liuqin, Jin, Chenxi, Huang, Jiawen, Deng, Wei, Wang, Congcong, Li, E, Hu, Yue, Tao, Zi, Li, Humingzhu, Yu, Xiang, Xu, Min, Chang, Hung-Chun, Zhang, Yifeng, Xu, Huatai, Yan, Jun, Li, Anan, Luo, Qingming, Stoop, Ron, Sternson, Scott M., Brning, Jens C., Anderson, David J., Poo, Mu-ming, Sun, Yidi, Xu, Shengjing, Gong, Hui, Sun, Yan-Gang, Xu, Xiaohong

Issue&Volume: 2025-03-26

Abstract: The hypothalamus coordinately regulates physiological homeostasis and innate behaviors, yet the detailed arrangement of hypothalamic axons remains unclear. Here we mapped the whole-brain projections of over 7,000 hypothalamic neurons expressing distinct neuropeptides in male mice, identifying 2 main classes and 31 types using single-neuron projectome analysis. These classes/types exhibited regionally biased soma distribution and specific neuropeptide enrichment. Notably, many projectome types extended long-range axon collaterals to distinct brain regions, allowing single axons to co-regulate multiple targets. We uncovered topographic organization of certain peptidergic axons at specific targets, along with diverse single-neuron projectome patterns in Orexin, Agrp and Pomc populations. Furthermore, hypothalamic peptidergic neurons showed correlated innervation of subdomains in the periaqueductal gray and organized into modular subnetworks within the hypothalamus, providing a structural basis for coordinated outputs. This dataset highlights the complexity of hypothalamic axonal projections and lays a foundation for future investigation of the circuit mechanisms underlying hypothalamic functions.

DOI: 10.1038/s41593-025-01919-0

Source: https://www.nature.com/articles/s41593-025-01919-0