An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents
An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents
复制标题
DOI：
10.1016/j.cell.2020.03.004
复制
发表时间：
2020-04-30
期刊：
影响因子：
64.5
通讯作者：
Liberles, Stephen D.
中科院分区：
文献类型：
--
作者：
Prescott, Sara L.;Umans, Benjamin D.;Liberles, Stephen D.
感觉神经元发起防御反射，确保气道完整性。喉部神经元功能障碍可危及生命，导致肺误吸、吞咽困难和窒息，但相关的感觉通路仍知之甚少。在这里，我们发现了罕见的喉咙支配神经元（类似于每只小鼠 100 个神经元），可以保护气道免受攻击。我们使用广泛覆盖迷走神经/舌咽感觉神经元图谱的遗传工具来绘制、消融和控制特定的传入群体。迷走神经 P2RY1 神经元的光遗传学激活会引发协调的气道防御程序——呼吸暂停、声带内收、吞咽和呼气反射。迷走神经 P2RY1 神经元的消融消除了对喉部水和酸挑战的保护性反应。解剖图显示了多种喉末端类型，其中 P2RY1 神经元形成小体末端，与喉味蕾并列。上皮细胞是初级气道哨兵，通过 ATP 与二级 P2RY1 神经元进行通信。这些发现提供了对气道防御的机制见解以及迷走神经内脏器官感觉的一般分子/遗传路线图。
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 (similar to 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.