Wang Tongtong, Teng Bochuan, Yao Dickson R, Gao Wei, Oka Yuki
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
Nature. 2025 Jan;637(8047):895-902. doi: 10.1038/s41586-024-08269-0. Epub 2024 Nov 27.
The autonomic nervous system orchestrates the functions of the brain and body through the sympathetic and parasympathetic pathways. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here we show topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified molecularly distinct sympathetic populations in the coeliac-superior mesenteric ganglia (CG-SMG). Of note, individual CG-SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG-SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons regulates gastrointestinal transit, and another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulation of visceral organ functions by sympathetic populations.
自主神经系统通过交感神经和副交感神经通路协调大脑和身体的功能。然而,我们在细胞和分子水平上对自主神经系统,尤其是交感神经系统的了解极为有限。在此,我们展示了主要腹部交感神经节复合体中各个内脏器官的拓扑表示。通过多模态转录组分析,我们在腹腔-肠系膜上神经节(CG-SMG)中鉴定出分子上不同的交感神经群体。值得注意的是,单个CG-SMG群体对内脏器官表现出选择性且相互排斥的轴突投射,靶向胃肠道或包括胰腺和胆道在内的分泌区域。这种组合式神经支配模式表明不同CG-SMG群体之间存在功能分隔。事实上,我们的神经扰动实验表明,一类神经元调节胃肠运输,另一类神经元独立于肠道蠕动控制消化和胰高血糖素分泌。这些结果揭示了分子多样化的交感神经系统,并表明交感神经群体对内脏器官功能进行模块化调节。