Modeling the role of the NTS in the neurogenesis of airway defensive behaviors

模拟 NTS 在气道防御行为神经发生中的作用

• 批准号: 9458386
• 负责人: DONALD C BOLSER
• 金额: $ 1.39万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9458386
• 关键词: Animal Model; Apnea; Area; Aspiration Pneumonia; Behavior; Biological Models; Biological Neural Networks; Blood gas; Brain; Brain Stem; Breathing; Carbon Dioxide; Cause of Death; Cells; Computer Simulation; Coughing; Data; Deglutition; Deglutition Disorders; Diagnosis; Disease; Dorsal; Elements; Goals; Human; Impairment; Infection; Knowledge; Laboratories; Life; Long-Term Care; Lung; Mediating; Modeling; Motor; Neural Network Simulation; Neuromuscular Diseases; Neurons; Nucleus solitarius; Outcome; Patients; Pattern; Phase; Physiological; Process; Reflex action; Regulation; Respiratory Muscles; Respiratory System; Role; System; Technology; Testing; Work; autonomic reflex; base; blood pressure regulation; experimental study; in vivo; mortality; nervous system disorder; network models; neurogenesis; neuromechanism; novel strategies; predictive modeling; protective behavior; relating to nervous system; respiratory; response; role model; simulation

PROJECT SUMMARY Various neuromuscular diseases result in impaired cough (dystussia). Disorders of these airway protective behaviors increase pulmonary infection due to aspiration, the leading cause of death in neuromuscular disease. Mortality rates of aspiration pneumonia - present in over half of long-term care residents - can approach 40%. Defense of the airway is achieved through coordination of multiple protective behaviors by brain circuits that remain incompletely understood. A contemporary data-driven computational model incorporating the brainstem network for breathing can rapidly reconfigure to produce the three phases a cough motor pattern: inspiration, compression, and expulsion. However, critical elements of airway protection cannot be explained. Based on motivating preliminary data and network simulations, we propose that a circuit in the nucleus of the solitary tract (NTS) and dorsal medulla regulates phase timing and respiratory muscle drive during paroxysmal coughs and exerts a command function over the brainstem respiratory control system to coordinate coughing and breathing. The project has 3 Specific Aims: (1) Determine dynamic behavior- dependent organization of NTS circuits during the expression of airway protective behaviors. (2) Determine functional connectivity between NTS and VRC neurons during expression of coughing. (3) Reconstruct our respiratory system model to incorporate regulation of both airway protective reflexes and breathing. Our unique approach, building upon experimental interrogation of the NTS region, incorporates multi-array recording technologies in an animal model system that generates defensive behaviors in response to physiologically relevant airway perturbations. We anticipate that the project will lead to: a) a new, predictive model of airway protection will be produced, b) we will understand functional relationships between conditionally active cells and t-E NTS neurons in producing cough, and c) we will identify critical NTS to parafacial/VRC functional relationships that regulate cough and breathing. This new knowledge will provide a critical step in understanding the neurogenesis of cough and how this behavior is controlled to protect the airway.

项目摘要 各种神经肌肉疾病导致咳嗽受损（肌无力）。这些气道保护性疾病 行为增加了由于吸入导致的肺部感染，这是神经肌肉疾病的主要死亡原因。 疾病吸入性肺炎的死亡率-超过一半的长期护理居民存在-可以 接近40%。气道的防御是通过多种保护行为的协调来实现的， 大脑回路仍然不完全了解。当代数据驱动的计算模型 将脑干网络整合到呼吸系统中， 运动模式：吸气、压缩和排出。然而，气道保护的关键要素不能 解释一下基于激励的初步数据和网络模拟，我们提出了一个电路，在 孤束核（NTS）和延髓背侧调节相位定时和呼吸肌驱动 并对脑干呼吸控制系统施加命令功能， 协调咳嗽和呼吸。该项目有3个具体目标：（1）确定动态行为- 呼吸道保护行为表达过程中NTS回路的依赖性组织。(2)确定 在咳嗽表达过程中NTS和VRC神经元之间的功能连接。(3)重建我们 呼吸系统模型，以纳入气道保护反射和呼吸的调节。我们独特 一种建立在NTS区域实验性询问基础上的方法，包括多阵列记录 动物模型系统中的技术，该系统响应于生理上的 相关气道扰动。我们预计，该项目将导致：a）一个新的，预测模型的气道 B）我们将理解条件活性细胞之间的功能关系 和t-E NTS神经元在产生咳嗽，和c）我们将确定关键的NTS旁/VRC功能 调节咳嗽和呼吸的关系。这一新知识将提供关键的一步， 了解咳嗽的神经发生以及如何控制这种行为以保护气道。