Neural control of breathing

呼吸的神经控制

• 批准号: 9900044
• 负责人: JACK L FELDMAN
• 金额: $ 78.17万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-11 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900044
• 关键词: Amyotrophic Lateral Sclerosis; Apnea; Area; Behavior; Birth; Blood gas; Brain; Brain Stem; Breathing; Cell Nucleus; Cessation of life; Data; Failure; Gases; Generations; Health; Human; Hyperventilation; In Vitro; Life; Light; Mammals; Mediating; Metabolism; Multiple System Atrophy; Muscle; Nervous system structure; Neurodegenerative Disorders; Neurons; Opsin; Optics; Parkinson Disease; Pathologic; Pattern; Periodicity; Regulation; Respiration; Respiration Disorders; Respiratory Muscles; Rett Syndrome; Rodent; Series; Site; Sleep Apnea Syndromes; Sudden infant death syndrome; Syndrome; Techniques; Viral; congenital central hypoventilation syndrome; designer receptors exclusively activated by designer drugs; experimental study; in vivo; neuromechanism; neuron loss; neuroregulation; preBotzinger complex; premature; public health relevance; respiratory

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.

项目摘要 呼吸是生命基础的非凡行为，它介导气体交换以支持新陈代谢和 调节pH。可靠的，不间断的，可靠的呼吸肌肉活动的节奏模式对于 在哺乳动物中呼吸。无法维持患有睡眠呼吸暂停的人的正常呼吸模式， 早产呼吸暂停，先天性中央中央低文化综合征，换气综合征，RETT综合征，RETT综合征， 也许是婴儿猝死综合症，导致严重的不良健康后果，甚至导致死亡。 各种神经退行性疾病，例如帕金森氏病，多种系统萎缩和肌萎缩症 横向硬化症与睡眠失调呼吸有关，我们假设因丧失 控制呼吸的大脑区域的神经元。如果要在正常和病理中理解呼吸 必须揭示条件，呼吸中心模式产生的机制。我们专注于两个大脑 对于生成正常呼吸模式，prebötzinger络合物和逆转录酶的必不可少的站点 细胞核/副呼吸组。我们在体内和体外提出了一系列广泛的实验 使用高级技术的啮齿动物，包括：传播以表达一般编码的Opsins或 这些地区神经元关键亚群中的恐怖症；高级光学技术来确定 Prebötzinger复合物微电路对节奏产生的贡献；最先进的神经解剖学 以适当和必要的细节建立脑干呼吸道的互连性的技术 模式生成器。这些实验的数据将为机制提供一个非凡的窗口 潜在的呼吸节奏和模式产生。