Computational Studies of the Respiratory Brainstem

描述（由申请人提供）：了解呼吸的控制是综合生物学和医学的一个重要目标。新生儿和成年人的睡眠障碍会干扰呼吸，这与肺动脉和全身性高血压以及其他疾病和风险的发展有关。该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。详细的生物物理学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，以测试基于模型的亚细胞、细胞、网络和系统水平机制的假设，这些机制在正常呼吸和过度通气性呼吸暂停之间、从正常呼吸到喘息以及在睡眠和清醒期间的过渡期间改变呼吸网络。实验反馈将用于迭代地调整模型。该项目有五个目标：1。开发腹外侧髓“核心”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式建模/实验研究的工具。2.评价延髓中央模式发生器（CPG）、脑桥呼吸组、孤束核和中缝核之间的相互作用。3.阐明与化学驱动和喘息的瞬时变化相关的网络重构和呼吸运动模式的机制。4.识别脑桥-延髓呼吸网络的输入，这些输入可以产生在睡眠-觉醒周期中观察到的呼吸运动模式，并且可以导致睡眠呼吸暂停。这些输入或它们的缺失最终导致睡眠障碍。5.测试生物物理，蜂窝和网络机制a）速率和同步“编码”和网络稳定性。该项目将汇集来自五个州的大学的研究人员。该小组的成员在呼吸控制、互补的专业领域、庞大且不断增长的实验数据库以及长期的学院关系方面有着共同的兴趣。该项目将促进先进的多阵列记录技术和计算方法、建模和仿真工具以及大型数据集的开发和共享。

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.