Functional mapping of peripheral and central circuits for airway protection and breathing

肺是为数不多的内脏器官之一，由自主(迷走神经)和躯体神经系统的传入和传出成分调节。自主神经成分涉及肺和呼吸道中的迷走神经感受器，以及呼吸道平滑肌或粘液分泌腺/细胞的传出神经支配。呼吸或保护呼吸道(咳嗽)所必需的躯体部分包括膈/横隔膜和附属(肋间、腹部)运动系统。这些传入和传出的自主神经/躯体系统由共享的脑干和脊髓网络协调，这些网络能够选择性地利用传入和传出成分来产生规律的呼吸或零星(触发)的呼吸道保护行为(例如咳嗽、喉内收肌反射)。呼吸系统由一个多尺度的感觉运动控制网络组成，表现出神经可塑性。在这个项目中，我们将研究呼吸系统的某些方面：1)对脊髓或脊髓感觉神经的电刺激，2)脑神经传入反馈的一过性扰动，3)间歇性低氧，4)呼吸道或全身炎症，5)影响呼吸和呼吸道防御的临床疾病检查。几个参与的实验室使用药理学、遗传学和解剖学方法，旨在了解调节呼吸道功能的迷走神经感觉通路。Cre小鼠将被用来描绘来自不同迷走神经节及其外周投射的呼吸道神经调节通路。我们还将通过阐明引起喉内收肌反射的中枢回路来研究负责呼吸道保护的神经机制。电刺激脊神经和/或脊髓可诱导膈感觉运动系统传入和传出通路的神经可塑性。我们在体内的努力将通过对感觉反馈和控制呼吸功能的中枢神经系统的计算建模来统一。这些建模工作包括第一次模拟喉内收肌反射和NTS通路，该通路整合了呼吸道机械感受器和C纤维反馈。

The lungs are one of the few visceral organs regulated by afferent and efferent components of both the autonomic (vagal) and somatic nervous systems. Autonomic components involve vagal sensory receptors in the lungs and airways, and efferent innervation of airway smooth muscle or mucus secreting glands/cells. Somatic components necessary to even take a breath or defend the airways (cough) include the phrenic/diaphragm and accessory (intercostal, abdominal) motor systems. These afferent and efferent autonomic/somatic systems are coordinated by shared brainstem and spinal cord networks capable of selectively utilizing afferent and efferent components to produce regular breathing, or sporadic (triggered) airway protective behaviors (e.g. cough, laryngeal adductor reflex). The respiratory system consists of a multiscale sensorimotor control network that exhibits neuroplasticity. In this project we will investigate selected aspects of the respiratory system by: 1) electrical stimulation of the spinal cord or spinal sensory nerves, 2) transient perturbations in afferent feedback from cranial nerves, 3) intermittent hypoxia, 4) airway or systemic inflammation and 5) examination of clinical disorders that compromise breathing and airway defense. Several of the participating labs employ pharmacological, genetic and anatomical methods aimed at understanding vagal sensory pathways that regulate airway function. CRE mice will be used to delineate airway neuromodulator pathways from distinct vagal ganglia and their peripheral projections. We also will investigate neural mechanisms responsible for airway protection by elucidation of central circuits that give rise to the laryngeal adductor reflex. Neuroplasticity in afferent and efferent pathways of the phrenic sensorimotor system will be induced by electrical stimulation of spinal nerves and/or spinal cord. Our in vivo efforts will be unified by computational modeling of the sensory feedback and central neural system that controls respiratory function. These modeling efforts include the first simulations of the laryngeal adductor reflex and the NTS pathways that integrate airway mechanoreceptor and C-fiber feedback.