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

Abstract 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.