Brainstem Respiratory Neuron Interactions

描述（由申请人提供）：了解产生和调节呼吸运动模式的脑干网络是生理学和医学的重要目标。干扰呼吸的障碍与肺和全身性高血压、婴儿猝死、学习障碍、帕金森病和自主神经功能障碍以及其他障碍和风险的发展相关，例如，中风和多发性硬化症延髓腹外侧区的神经网络被认为是产生呼吸运动模式所必需的。其他脑干部位用来调节这个网络的回路尚不清楚。该项目的主要假设是：外周和中枢化学感受器通过一个分布式网络调节呼吸运动模式，该网络包括“脑桥呼吸组”（PRG）、延髓中缝核和蓝斑中的多功能神经元。该项目有四个具体目标： 1.定义脑桥呼吸组（PRG）内以及PRG与核心延髓呼吸网络之间的功能回路。 2.定义PRG的功能回路和核心延髓呼吸网络，适用于中枢和外周化学感受器驱动变化期间呼吸运动模式的调制。 3.定义对中枢和外周化学感受器驱动变化做出反应的中缝神经元的功能连接，包括中缝系统与PRG和核心髓网络之间的功能回路。 4.识别蓝斑神经元对中枢和外周化学感受器驱动变化的反应功能回路及其与其他调节域和核心延髓呼吸网络的功能连接。该项目将使用多阵列记录和计算方法来定义功能电路及其在改变呼吸的化学感受器挑战期间的反应。结果将导致新的网络模型的呼吸脑干在正常和病理生理条件。

DESCRIPTION (provided by applicant): Understanding the brainstem network that generates and modulates the respiratory motor pattern is an important goal in physiology and medicine. Disorders that disrupt breathing are associated with the development of pulmonary and systemic hypertension, sudden infant death, learning disabilities, Parkinson's disease and autonomic dysfunction, and other disorders and risks, e.g., stroke and multiple sclerosis. A neural network in the ventrolateral medulla is considered essential for generating the respiratory motor pattern. The circuits used by other brainstem sites to modulate this network are not known. The primary hypothesis of this project is: Peripheral and central chemoreceptors modulate the respiratory motor pattern through a distributed network that includes multifunctional neurons in the "pontine respiratory group" (PRG), the medullary raphe nuclei, and the locus ceruleus. The project has four specific aims: 1. Define functional circuits within the pontine respiratory group (PRG) and between the PRG and the core medullary respiratory network. 2. Define the functional circuits of the PRG and the core medullary respiratory network appropriate for modulation of the respiratory motor pattern during changes in central and peripheral chemoreceptor drive. 3. Define the functional connectivity of raphe neurons that respond to changes in central and peripheral chemoreceptor drive, including functional circuits between the raphe system and the PRG and core medullary networks. 4. Identify functional circuits of locus ceruleus neurons that respond to changes in central and peripheral chemoreceptor drive and their functional connectivity with other modulatory domains and the core medullary respiratory network. The project will use multi-array recordings and computational methods to define functional circuits and their responses during chemoreceptor challenges that alter breathing. The results will lead to new network models of the respiratory brainstem in both normal and pathophysiological conditions.