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, Brüning Jens C, Anderson David J, Poo Mu-Ming, Sun Yidi, Xu Shengjing, Gong Hui, Sun Yan-Gang, Xu Xiaohong
Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Neurosci. 2025 May;28(5):1073-1088. doi: 10.1038/s41593-025-01919-0. Epub 2025 Mar 26.
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.
下丘脑协调调节生理稳态和先天行为，然而下丘脑轴突的详细排列仍不清楚。在这里，我们绘制了雄性小鼠中表达不同神经肽的7000多个下丘脑神经元的全脑投射图谱，通过单神经元投射组分析确定了2个主要类别和31种类型。这些类别/类型表现出区域偏向性的胞体分布和特定神经肽富集。值得注意的是，许多投射组类型将长距离轴突侧支延伸到不同的脑区，使单个轴突能够共同调节多个靶点。我们发现了特定肽能轴突在特定靶点的拓扑组织，以及食欲素、刺鼠肽基因相关蛋白和阿黑皮素原群体中多样的单神经元投射组模式。此外，下丘脑肽能神经元在导水管周围灰质的亚区域显示出相关的神经支配，并在下丘脑内组织成模块化子网，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，并为未来研究下丘脑功能背后的神经回路机制奠定了基础。
