A pharynx-to-brain sensory pathway mediates swallowing-like behavior evoked by mechanical stimulation

As sharing the anatomical entrance to the larynx, swallowing plays not only an important role in food and water intake, but also a major role in defensive mechanism for preventing the risk of foreign matter aspiration. Besides water/acid, the mechanical stimulation of food or foreign matter could induce swallowing, yet the relevant sensory pathways remain poorly understood. Here, using male mice as a model, we clarify that vagal sensory neurons expressing Piezo2 responsibly transmit swallowing induced mechanical stimuli from the pharynx to tyrosine hydroxylase positive (TH + ) neurons in the nucleus of the solitary tract (NTS), then to ambiguus nucleus/rostral ventrolateral medulla (Amb/RVLM complex).

Specific activation of Piezo2+ vagal sensory neurons or TH + NTS neurons can induce swallowing behavior. Either inhibition of TH + NTS neurons or Piezo2 knockout in vagal sensory neurons can abolish swallowing reflex. Notably, we elucidate that the TH + NTS-Amb/RVLM pathway serves as a shared downstream pathway for both mechanical and chemical stimuli-elicited swallowing.

Collectively, we describe a pharynx-to-brain sensory pathway that provides a basis for central integration of swallowing and airway defensive reflexes. We thank D.L., C.S. and W.Z. for their assistance with the development of customized code and X.L., for your assistance with bioinformatics analysis. This work is supported by the National Natural Science Foundation of China (32422032 and 32271069 to C.S.), Major Project of Guangzhou National Laboratory (MP-GZNL2024A02001-02 and Grant No.

GZNL2024A02001 to C.S.), Guangdong special support plan (2023TQ07A609 to C.S.). All data are archived in Guangzhou National Laboratory. These authors contributed equally: Qing Pei, Lifang Huo.

School of Life Sciences, Sun Yat-Sen University, Guangzhou, China School of Basic Medical Sciences, The Fifth Affiliated Hospital, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou, China Qing Pei, Lifang Huo, Jie Cao, Xingxing Lai, Zhimin Ye & Congping Shang Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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