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一个重要目标。干扰呼吸的疾病与发生肺和全身高血压、婴儿猝死、学习障碍、帕金森氏病和自主神经功能障碍以及其他疾病和风险有关，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一网络的电路尚不清楚。这个项目的基本假设是：外周和中枢化学感受器通过一个分布的网络调节呼吸运动模式，该网络包括“桥呼吸群”(PRG)、延髓中缝核和蓝斑的多功能神经元。该项目有四个具体目标： 1.确定脑桥呼吸组(PRG)内以及PRG和核心延髓呼吸网之间的功能回路。 2.确定在中枢和外周化学感受器驱动改变时，适合调节呼吸运动模式的PRG和核心延髓呼吸网络的功能回路。 3.确定对中枢和外周化学感受器驱动变化作出反应的中缝神经元的功能连接，包括中缝系统和PRG之间的功能电路以及核心延髓网络。 4.确定蓝斑神经元对中枢和外周化学感受器驱动的变化作出反应的功能回路，以及它们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化学感受器挑战期间改变呼吸的反应。这一结果将导致在正常和病理生理条件下建立新的呼吸脑干网络模型。

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.