NEURONAL AND CHEMICAL CONTROL OF BREATHING AN AIRWAYS FU

足够的气体交换和足够的02供应到组织依赖于气道的通畅，气道是由中枢和周围神经系统调节的。霍华德大学对RFA的回应是基于对呼吸和气道功能的中枢和外周神经控制的基础研究的需要；包括嗅觉。不同组织水平的感觉和/或运动神经支配改变的后果是神经元调节机制的紊乱，可能导致严重的健康问题。为了解决这些问题，我们提出了四个相互关联的项目。项目1将通过研究调节快速眼动（REM）和安静（非REM）睡眠的中枢神经系统位点如何对呼吸相关的骨骼和气道平滑肌施加不同的控制，来确定行为变化过程中呼吸和气道不稳定的主要决定因素。项目2将研究中枢化学感受器神经元的神经化学特征，它们的受体类型，以及它们对呼吸和气道相关运动神经元的神经元投射。项目3将研究嗅觉系统可塑性的基因调控，以及对物理、化学和生物应激源的急性期反应中的信号传导。项目4将研究由环境因子触发的气道感觉神经支配和基因调控机制的作用，环境因子以前驱方式作用，增强气道炎症和支气管收缩，以及与气道高反应性、气道狭窄和气道扩张影响的难治性相关的信号系统的改变。这些研究将采用新的调查方法来回答问题，这些问题将增强我们对呼吸和气道功能调节的基本机制的理解。此外，从霍华德大学研究界以外组建一个多学科科学家团队将使我们能够产生新的信息，这将促进知识的发展，并提出有关未来研究的相关问题。这一提议体现了医学院的承诺，即投资基础设施并保证长期支持，将有才华的研究人员聚集在一起。大学承诺为该计划的参与者提供适当的释放时间来进行本文所述的研究。

An adequate gas exchange and a sufficient supply of 02 to tissues depends on the patency of the airways which are regulated by central and peripheral nervous systems. The Howard University response to this RFA is based on the need for fundamental research in regard to central and peripheral nervous control of breathing and airway functions; including olfaction. Disturbances in neuronal regulatory mechanisms, as a consequences of alterations in sensory and/or motor innervations at different levels of organization, may cause serious health problems. To address some of these issues, we propose four interrelated projects. Project 1 will define central determinants of breathing and airway instability during behavioral changes by examining how CNS sites that regulate rapid eye movements (REM) and quiet (non-REM sleep might exert a differential control on respiratory related skeletal and airway smooth muscles. project 2 will study the neurochemical profile of the central chemoreceptor neurons, their receptor types, as well as their neuronal projections to respiratory and airway related motoneurons. Project 3 will investigate gene regulation involved in plasticity of the olfactory system as well as signaling during the acute phase response to physical, chemical and biological stressors. Project 4 will investigate the role of sensory innervation of the airway and gene regulatory mechanisms triggered by environmental agents, which operate in a feed forward manner enhancing airway inflammation and bronchoconstriction, and alterations in the signaling system linked to airway hyper-reactivity, airway narrowing and refractoriness to airway dilating influences. New investigative approaches will be used in these studies to answer questions which will enhance our understanding of the fundamental mechanisms underlying regulation of respiratory and airway functions. Furthermore, assembling a team of multi-disciplinary scientists from outside of the Howard University research community will enable us to generate new information that will advance knowledge, and ask relevant questions regarding future studies. This proposal is an expression of the commitments made by the College of Medicine, investing in infrastructure and guaranteeing long-term support, to bring talented researchers to work together. The university is committed to provide appropriate release time for the participants in this program to perform the research described herein.