HYPOTHALAMIC REGULATION OF RESPIRATION DURING SLEEP

睡眠期间下丘脑的呼吸调节

• 批准号: 6505105
• 负责人: DENNIS J MCGINTY
• 金额: $ 26.66万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6505105
• 关键词: arousal; brain electrical activity; cats; electroencephalography; electromyography; hypothalamus; muscle tone; neuroregulation; preoptic areas; pulmonary respiration; respiratory muscles; sleep apnea; sleep regulatory center

Much evidence supports a hypothesis that hypothalamic preoptic area (POA) temperature-sensitive neurons play a critical role in the regulation of NREM sleep, as a component of overall metabolic regulation. The activation of POA warm sensitive neurons is necessary and sufficient for initiation of NREM sleep. The hypnogenic output from the POA is hypothesized to be a descending gamma-aminobutyric acid (GABA)ergic pathway which inhibits arousal-promoting systems in the posterior hypothalamus (PH) and brainstem. In PH, a GABA-regulated system facilitates respiratory motor and autonomic responses. We hypothesize that PH respiratory mechanisms are coupled to PH arousal generating mechanisms, and that arousal induced respiratory facilitation originating in the PH is a critical component of the wakefulness-drive to-breathing. We propose a model in which this drive is actively inhibited during sleep, that this inhibition originates in the POA, and is mediated by GABAergic inhibitory projections from the POA to the PH. The proposed studies will examine hypothesis central to this model. Activation of POA warm-sensitive neurons will 1) suppress diaphragmatic and upper airway dilator activity during sleep and 2) suppress discharge of PH neurons in chronic animals, via a GABAergic process. 3) POA warming will reduce respiratory coupling of medullary reticular neurons. POA cooling will have opposite effects. Obstructive sleep apnea are characterize by sleep onset-induced airway dilator and respiratory pump muscle deactivation. These events are thought to be consequences of the loss of the wakefulness-drive-to-breathing. In addition, many patients exhibit reduced arousal responses and reduced compensation for airway resistance, Thus, we hypothesize that arousal dysregulation is part of the disease. We hypothesize that excessive energy conservation drive, originating in the POA, induces sleepiness and respiratory motor deactivation at sleep onset.

下丘脑视前区（POA）是视神经系统的重要组成部分。 温度敏感神经元在调节神经元的活动中起着关键作用。 NREM睡眠，作为整体代谢调节的组成部分。激活 POA温敏神经元的数量是启动的必要和充分条件 NREM睡眠。POA的催眠输出被假设为 下行γ-氨基丁酸（GABA）能通路，其抑制 下丘脑后部（PH）的唤醒促进系统， 脑干在PH中，GABA调节系统促进呼吸运动 和自主反应。我们假设PH呼吸机制是 再加上PH唤醒产生机制， 起源于PH的呼吸促进是 觉醒驱动呼吸。我们提出了一个模型，在这个模型中， 在睡眠期间被积极抑制，这种抑制起源于 POA，并介导GABA能抑制性投射从POA到 药典 拟议中的研究将检验这一模型的核心假设。 POA温敏神经元的激活将1）抑制 和睡眠期间的上呼吸道扩张器活动，以及2）抑制放电 PH神经元的慢性动物，通过γ-氨基丁酸能过程。3)POA变暖 将减少延髓网状神经元的呼吸耦合。POA 冷却将具有相反的效果。 阻塞性睡眠呼吸暂停是以睡眠发作引起气道阻塞为特征 扩张器和呼吸泵肌肉失活。这些事件被认为 是因为失去了对呼吸的清醒驱动力。在 此外，许多患者表现出降低的唤醒反应和降低的 因此，我们假设， 失调是疾病的一部分我们假设过多的能量 起源于POA的保护驱动，引起嗜睡， 睡眠开始时呼吸运动失活。