MECHANISMS OF PHASIC RESPIRATORY PHENOMENA IN REM SLEEP

快速眼动睡眠阶段性呼吸现象的机制

• 批准号: 6109968
• 负责人: Allan I Pack
• 金额: $ 15.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6109968
• 关键词: REM sleep; afferent nerve; auditory stimulus; behavior test; brain electrical activity; cats; diaphragm; electroencephalography; electromyography; electrooculography; electrophysiology; experimental brain lesion; gamma aminobutyrate; microinjections; neurochemistry; norepinephrine; pons; pulmonary respiration; respiration regulatory center; serotonin; sleep apnea; startle reaction; tegmentum

Major changes take place in the output to respiratory pump and upper airway muscles in association with the phasic events of REM sleep. These phasic changes have adverse consequences and initiate apneas in REM sleep. The overall goal of this proposal is to investigate the neural mechanisms producing these phasic respiratory phenomena. Our attention is directed to the pedunculopontine tegmental (PPT) nucleus in the pons. Lesions of this area abolish ponto-geniculo-occipital (PGO) waves that occur phasically in REM sleep. PGO waves are temporally linked to the phasic changes in respiration in REM sleep. Our goal is to determine the role of neurons in this area in generation of the phasic respiratory phenomena in REM sleep. The first protocol involves lesioning the area by neurotoxic chemicals and examining the effect on PGO waves and respiratory phasic phenomena. If, as we postulate, this area is critical to generating the phasic-changes in respiratory motor output, they should be abolished or markedly reduced in frequency by such lesions. PGO waves and alteration in diaphragm output can also be produced by alerting stimuli; this has led to the concept that there is endogenous activation of the startle system in REM sleep. Thus, in this protocol we will also determine whether lesions of the PPT abolish the PGO and respiratory response to alerting stimuli. In a second series of studies, we will apply complimentary techniques. These will be based on manipulating the neurochemical environment of the region. There are different theories as to what modulates burst neurons that generate PGO waves. One theory implicates serotonin from the dorsal raphe, another serotonin and noradrenaline from locus coeruleus, while a third proposes that GABA from substania nigra plays the major role. The studies we propose will directly test each of these hypotheses. In each case we will administer antagonists in non-REM states to see if we can induce PGO waves and associated phasic respiratory phenomena. Agonists will be administered in REM sleep to see if PGO wave production and phasic respiratory changes can be blocked. Such studies will both enhance our understanding of the role of this area in generating phasic respiratory phenomenon and the fundamental mechanism controlling these phasic generators. Activity of these neural generators must be relayed to the respiratory motor outputs. There are both ascending and descending projections from the area. In order to begin to establish which of these is likely to mediate the respiratory effects, we will, in a third series of protocols, study the effect of interrupting the descending projections on phasic respiratory events. Because activity of neurons in the PPT may also be affected by sleep disruption, the final protocol will address whether a vicious cycle exists whereby interruption of REM sleep leads to more phasic respiratory phenomena. These studies are, therefore, a comprehensive investigation of the mechanism generating phasic respiratory change in REM sleep, their neurochemical control and their relevance to sleep apnea syndrome.

输出对呼吸泵和上部发生了重大变化 气道肌肉与REM睡眠的阶段性事件相关。这些 阶段变化具有不良后果，并在REM睡眠中启动呼吸暂停。 该提案的总体目标是调查神经机制 产生这些阶段性呼吸现象。我们的注意力集中在 PON中的花梗齿状细胞核（PPT）核。病变 地区废除蓬托基因甲基枕（PGO）波，该波发生在物理中 REM睡觉。 PGO波在时间上与阶段变化有关 REM睡眠中的呼吸。我们的目标是确定神经元在 该区域是REM睡眠中阶段性呼吸现象的产生。 第一个方案涉及通过神经毒性化学物质和 检查对PGO波和呼吸阶段现象的影响。如果， 我们假设，该区域对于在 呼吸运动输出，应废除或明显减少 通过这种病变的频率。 PGO波和隔膜输出的改变 也可以通过警告刺激来产生；这导致了这样一个概念 REM睡眠中的惊吓系统存在内源性激活。因此， 在此协议中，我们还将确定PPT病变是否废除 对警报刺激的PGO和呼吸反应。在第二个系列中 在研究中，我们将采用免费技术。这些将基于 操纵该地区的神经化学环境。有 关于调节产生PGO的突发神经元的不同理论 波浪。一种理论暗示了背raphe的5-羟色胺，另一种理论 5-羟色胺和去甲肾上腺素来自基因座，而三分之一提出 Nigra的GABA起着主要作用。我们的研究 建议将直接检验这些假设中的每一个。在每种情况下，我们都会 在非REM状态下进行拮抗剂，以查看我们是否可以诱导PGO波 和相关的呼吸道现象。激动剂将被管理 在REM睡眠中，查看PGO波的产生和阶段性呼吸是否改变 可以阻止。 这样的研究都将增强我们对 该领域在产生阶段呼吸道现象和 控制这些阶段发电机的基本机制。活动的活动 这些神经发电机必须传递到呼吸运动输出。 该地区都有上升和下降的预测。在 为了开始建立哪个可能调解哪个 呼吸效应，我们将在第三个方案中研究 中断下降预测对阶段呼吸道的影响 事件。因为PPT中神经元的活动也可能受到 睡眠中断，最终协议将解决是否有恶性循环 存在REM睡眠的中断会导致更多的阶段性呼吸道 现象。因此，这些研究是对 在REM睡眠中产生阶段性呼吸道变化的机制 神经化学控制及其与睡眠呼吸暂停综合征的相关性。