Neural control of breathing

项目总结 呼吸是生命的一种重要行为，它调节气体交换以支持新陈代谢和 调节pH值。一个可靠的、不间断的、强健的呼吸肌活动节奏模式对于 哺乳动物的呼吸。睡眠呼吸暂停患者未能维持正常呼吸模式， 早产儿呼吸暂停，先天性中枢低通气综合征，过度呼吸综合征，雷特综合征， 也许还有婴儿猝死综合症，会导致严重的健康不良后果，甚至死亡。 各种神经退行性疾病，如帕金森氏病、多系统萎缩和肌营养不良 侧索硬化症与睡眠呼吸障碍有关，我们推测这种呼吸障碍是由于睡眠障碍 控制呼吸的大脑区域的神经元。如果要用正常和病理来理解呼吸 在这种情况下，必须揭示呼吸中枢模式产生的机制。我们关注的是两个大脑 正常呼吸模式、Prebötzinger复合体和后梯形呼吸模式的产生所必需的部位 核团/面旁呼吸组。我们提出了一系列广泛的体内和体外实验 使用先进技术的啮齿动物，包括：病毒递送表达基因编码的视蛋白或 这些区域的关键神经元亚群中的DREADD；先进的光学技术来确定 Prebötzinger复合微电路对节律产生的贡献；最先进的神经解剖学 以适当和必要的细节建立脑干呼吸的互连的技术 图案生成器。这些实验的数据将为了解这些机制提供一个非同寻常的窗口 潜在的呼吸节律和模式生成。

PROJECT SUMMARY Breathing is a remarkable behavior fundamental to life that mediates gas exchange to support metabolism and regulate pH. A reliable, non-stop, robust rhythmic pattern of respiratory muscle activity is essential for breathing in mammals. Failure to maintain a normal breathing pattern in humans suffering from sleep apnea, apnea of prematurity, congenital central hypoventilation syndrome, hyperventilation syndrome, Rett syndrome, and perhaps Sudden Infant Death Syndrome, leads to serious adverse health consequences, even death. Various neurodegenerative diseases, such as Parkinson's disease, multiple systems atrophy, and amyotrophic lateral sclerosis, are associated with sleep disordered breathing that we hypothesize results from the loss of neurons in brain areas controlling respiration. If breathing is to be understood in normal and in pathological conditions, the mechanisms for respiratory central pattern generation must be revealed. We focus on two brain sites essential for generation of the normal breathing pattern, the preBötzinger Complex and the retrotrapezoid nucleus/parafacial respiratory group. We propose a broad series of experiments both in vivo and in vitro in rodents using advanced techniques including: viral delivery to express genetically encoded opsins or DREADDs in key subpopulations of neurons in these regions; advanced optical techniques to determine the contributions of the preBötzinger Complex microcircuit to rhythm generation; state-of-the-art neuroanatomical techniques to establish, in appropriate and necessary detail, the interconnectivity of the brainstem respiratory pattern generator. The data from these experiments will provide an extraordinary window into the mechanisms underlying respiratory rhythm and pattern generation.