Abstract
The autonomic nervous system (ANS) plays a pivotal role in regulating organ functions through descending brain-to-body signalling. The pathways involved are broadly categorized into two major branches: the sympathetic nervous system, which mediates ‘fight or flight’ responses, and the parasympathetic nervous system, which governs ‘rest and digest’ functions. Historically, the ANS was considered to mediate simple motor functions with limited neurochemical diversity. However, recent advances in neurotechnology have shown that brain-to-body communication is more complex and dynamic than previously appreciated. This review synthesizes current knowledge about the molecular, anatomical and functional diversity of autonomic motor neurons. Here we present a comparative analysis of the cellular architecture of the ANS and the suggested roles of distinct neuron populations. Additionally, we explore the emerging view that the ANS interacts with diverse systems involving metabolism, immunology and ageing, which extends its role beyond simple brain–organ modulation. Finally, we emphasize the need for cell-type-specific and longitudinal studies of the ANS to uncover novel mechanisms underlying body–brain interactions and to identify new translational opportunities for therapeutic interventions.
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Data availability
We developed an online portal (available at https://ans-cell-atlas.com/) for an integrated view of published single-cell transcriptomics at the GEO database. All source code is available via GitHub at https://github.com/YTwTJ/Molecular-and-Functional-Diversity-of-the-Autonomic-Nervous-System. In Fig. 3, dot plots are generated from GEO datasets: SCG (GSE175421), stellate ganglion (GSE231924), CG-SMG (GSE278457), DMV (GSE172411) and nucleus ambiguus (GSE198709, GSE202760 and GSE211538). In Fig. 3, heat maps plot transcriptomic data available via the Human Protein Atlas at https://www.proteinatlas.org/humanproteome/tissue/data#hpa_tissues_rna.
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Acknowledgements
We thank the members of the Oka lab for helpful discussion and comments. Y.O. is supported by Startup funds from the President and Provost of California Institute of Technology, the Biology and Biological Engineering Division of California Institute of Technology, the New York Stem Cell Foundation, the Alfred P. Sloan Foundation, the Edward Mallinckrodt Foundation, and Heritage Medical Research Institute.
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T.W. researched data for the article. T.W. and A.T. developed transcriptomic data visualization portal. O.A.A. wrote the translational implications section. T.W. and Y.O. conceived and wrote the article.
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Wang, T., Tufenkjian, A., Ajijola, O.A. et al. Molecular and functional diversity of the autonomic nervous system. Nat. Rev. Neurosci. 26, 607–622 (2025). https://doi.org/10.1038/s41583-025-00941-2
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DOI: https://doi.org/10.1038/s41583-025-00941-2
