Details

Autor(en) / Beteiligte

• Prescott, Sara L.
• Umans, Benjamin D.
• Williams, Erika K.
• Brust, Rachael D.
• Liberles, Stephen D.

Titel

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

Ist Teil von

• Cell, 2020-04, Vol.181 (3), p.574-589.e14

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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 (∼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. [Display omitted] •Broad genetic access enables functional dissection of a vagal sensory neuron atlas•Rare P2RY1 sensory neurons guard the airways by engaging an airway defense program•P2RY1 neurons innervate the laryngeal epithelium and appose laryngeal taste buds•Epithelial cells detect laryngeal water/acid and communicate to P2RY1 neurons via ATP Prescott and colleagues reveal a rare population of vagal sensory neurons that serve as a first-line defense in the upper airways to prevent infiltration and injury within the respiratory tract. The authors develop an expansive genetic toolkit that broadly covers a vagal/glossopharyngeal sensory neuron atlas and use genetic approaches to map, ablate, and control vagal sensory neuron populations, revealing sensory neurons that receive input from laryngeal epithelial cells through ATP and in response mediate critical aspects of airway defense.