Computational Studies of the Respiratory Brainstem

描述(申请人提供)：了解呼吸的控制是生物学和医学综合的一个重要目标。新生儿和成年人的睡眠障碍会扰乱呼吸，这与肺和全身高血压以及其他障碍和风险的发展有关。这个合作项目的目标是开发脑干呼吸网络的统一模型，并确定异常可能扰乱呼吸及其控制的潜在部位。详细的生物物理和大规模模拟将指导相关的体内和体外神经生理学和药理学实验，以测试基于模型的假说，这些假说涉及亚细胞、细胞、网络和系统水平的机制，这些机制在真呼吸暂停和过度呼吸暂停之间的转变、从真呼吸暂停到喘息以及在睡眠和清醒期间改变呼吸网络。实验反馈将被用来反复调整模型。该项目有五个目标：1.开发延髓腹外侧核呼吸网络的综合计算模型，并将其用作呼吸神经控制的交互建模/实验研究的工具。2.评估延髓中枢模式发生器(CPG)、桥脑呼吸群、孤束核和中缝核团之间的相互作用。3.阐明网络重构的潜在机制，以及与化学驱动和喘息的瞬时变化相关的呼吸运动模式。4.确定脑桥-延髓呼吸网络的输入，它可以产生在睡眠-觉醒周期中观察到的呼吸运动模式，并可能导致睡眠呼吸暂停。这些输入或缺失是睡眠障碍的最终原因。5.测试生物物理、蜂窝和网络机制，以获得a)速率和同步“编码”以及网络稳定性。该项目将汇集来自五个州大学的研究人员。该小组的成员在呼吸控制、互补的专业知识领域、大型且不断增长的实验数据库以及长期的合作关系方面有着共同的兴趣。该项目将成为先进的多阵列记录技术和计算方法、建模和模拟工具以及大型数据集的开发和共享的催化剂。

DESCRIPTION (provided by applicant): Understanding the control of breathing is an important goal in integrative biology and medicine. Sleep disorders in newborns and adults that disrupt breathing have been implicated in the development of pulmonary and systemic hypertension and other disorders and risks. The goal of this collaborative project is to develop a unified model of the brainstem respiratory network and to identify potential sites where abnormalities can disrupt breathing and its control. Detailed biophysical and large-scale simulations will guide associated in vivo and in vitro neurophysiological and pharmacological experiments to test model-based hypotheses on sub-cellular, cellular, network and systems level mechanisms that transform the respiratory network during the transitions between eupnea and hyperventilation apnea, from eupnea to gasping, and during sleep and waking. Experimental feedback will be used to iteratively tune the model. The project has five aims: 1. Develop a comprehensive computational model of the ventrolateral medullary "core" respiratory network and use it as a tool for interactive modeling/experimental studies on the neural control of breathing. 2. Evaluate interactions among the medullary central pattern generator (CPG), the pontine respiratory group, the nuclei of the solitary tract, and the raphe nuclei. 3. Elucidate mechanisms underlying network reconfiguration and the respiratory motor patterns associated with transient changes in chemical drive and gasping. 4. Identify inputs to the pontine-medullary respiratory network that can produce the respiratory motor patterns observed during the sleep-wake cycle and that can cause sleep apnea. These inputs or their absence are ultimately responsible for sleep disorders. 5. Test biophysical, cellular, and network mechanisms for a) rate and synchrony "coding" and network stability. This project will bring together researchers from universities in five states. Members of the group have a common interest in the control of breathing, complementary areas of expertise, large and growing experimental databases, and long-standing collegial relationships. The project will be a catalyst for the development and sharing of advanced multi-array recording technologies and computational methods, modeling and simulation tools, and large data sets.