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Publication : An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents.

First Author  Prescott SL Year  2020
Journal  Cell Volume  181
Issue  3 Pages  574-589.e14
PubMed ID  32259485 Mgi Jnum  J:298576
Mgi Id  MGI:6442046 Doi  10.1016/j.cell.2020.03.004
Citation  Prescott SL, et al. (2020) An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents. Cell 181(3):574-589.e14
abstractText  Sensory neurons initiate defensive reflexes that ensure airway integrity. Dysfunction of laryngeal neurons is life-threatening, causing pulmonary aspiration, dysphagia, and choking, yet relevant sensory pathways remain poorly understood. Here, we discover rare throat-innervating neurons ( approximately 100 neurons/mouse) that guard the airways against assault. We used genetic tools that broadly cover a vagal/glossopharyngeal sensory neuron atlas to map, ablate, and control specific afferent populations. Optogenetic activation of vagal P2RY1 neurons evokes a coordinated airway defense program-apnea, vocal fold adduction, swallowing, and expiratory reflexes. Ablation of vagal P2RY1 neurons eliminates protective responses to laryngeal water and acid challenge. Anatomical mapping revealed numerous laryngeal terminal types, with P2RY1 neurons forming corpuscular endings that appose laryngeal taste buds. Epithelial cells are primary airway sentinels that communicate with second-order P2RY1 neurons through ATP. These findings provide mechanistic insights into airway defense and a general molecular/genetic roadmap for internal organ sensation by the vagus nerve.
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