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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要各种神经肌肉疾病会导致咳嗽受损（发音困难）。这些气道保护功能障碍行为会增加因误吸引起的肺部感染，这是神经肌肉疾病患者死亡的主要原因疾病。吸入性肺炎的死亡率 - 超过一半的长期护理居民 - 可能会增加接近40%。气道的防御是通过协调多种保护行为来实现的尚未完全了解的大脑回路。当代数据驱动的计算模型结合脑干呼吸网络可以快速重新配置以产生咳嗽的三个阶段运动模式：吸气、压缩和排出。然而，气道保护的关键要素不能予以解释。基于初步数据和网络仿真，我们提出了一种电路孤束核 (NTS) 和背髓质调节时相计时和呼吸肌驱动在阵发性咳嗽期间，并对脑干呼吸控制系统发挥指挥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 - NTS 回路在气道保护行为表达过程中的依赖组织。 (2)确定咳嗽表达过程中 NTS 和 VRC 神经元之间的功能连接。 (3)重建我们的呼吸系统模型结合了气道保护反射和呼吸的调节。我们独特的方法以 NTS 区域的实验询问为基础，结合了多阵列记录动物模型系统中的技术可根据生理反应产生防御行为相关气道扰动。我们预计该项目将带来：a) 一种新的气道预测模型将产生保护，b）我们将了解条件活跃细胞之间的功能关系和 t-E NTS 神经元在产生咳嗽中的作用，并且 c) 我们将识别对面旁/VRC 功能至关重要的 NTS 调节咳嗽和呼吸的关系。这些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。