NEURAL INHIBITION AND REM SLEEP DISORDERED BREATHING

睡眠呼吸紊乱(SDB)是一种广泛存在的严重疾病 以间歇性、重复性的缺氧为特征 睡吧。在大多数患者中，呼吸紊乱是最严重的 在快速眼动睡眠(REMS)期间。我们会研究 英语快速眼动时SDB的中枢神经机制 斗牛犬，他们有一种自然发生的，通常是严重的形式 和对照犬(小猎犬)。基于以前的 研究和初步数据，我们认为间歇性 呼吸肌抑制在慢性阻塞性肺疾病中起重要作用 在REMS期间。此外，上半部分的非同步抑制 呼吸道和横隔肌也可能导致梗阻 作为中枢性呼吸暂停。间歇性抑制在SDB中的作用 在长期使用仪器的、自由移动的狗身上进行研究。这个 产生间歇性抑制的中枢机制 对于阶段性事件，如眼球运动，将由 剖析惊吓反应和惊吓反应之间的关系 阶段性事件。惊吓事件和阶段性事件之间的联系 是因为自发的和诱发的神经生理学 REMS期间的事件类似于由令人震惊的 刺激物。在长期使用仪器的狗身上，我们将通过实验 改变惊吓反应，然后测量 REMS期间的间歇性抑制，寻找平行或 相关变化。我们还将研究 斗牛犬幼犬呼吸肌抑制和惊吓反应 和控制来确定增强的惊吓反应 导致了深发展的发展。我们将延长初步的 有证据表明睡眠不足和缺氧会增加惊吓- 在REMS过程中诱导肌肉抑制。增广的结果 抑制(SDB)，因此既会加强抑制，又会 造成恶性循环。拟议的研究还将尝试 通过第一次以离散的方式干预来缓解SDB 中枢神经系统的解剖区域。中介肌肉的通路 REMS期间的抑制局限于双侧的一小块区域 脑桥被盖。这一区域的损伤可以消除肌肉 抑制和，我们建议，缓解SDB通过增加对 快速呼吸综合征时的呼吸肌。最后，我们将开始研究， 第一次，伴随着SDB的神经化学变化 对斗牛犬和对照犬脑桥区的研究 定量密度测量和放射自显影，以定位和 量化特定的神经递质。这些研究应该提供 与进程相关的重要信息， SDB的病理生理和神经化学。

Sleep-disordered breathing (SDB) is a widespread, serious disease characterized intermittent, repetitive episodes of hypoxia during sleep. In most patients, the respiratory disturbances are worst during rapid eye movement sleep (REMS). We will study the central neural mechanisms of SDB during REMS in English Bulldogs, who have a naturally occurring and usually severe form of this disease, and control dogs (beagles). Based on previous studies and preliminary data, we propose that intermittent respiratory muscle inhibition plays an important role in SDB during REMS. Furthermore, asynchronous inhibition of upper airway and diaphragmatic muscles may lead to obstructive as well as central apneas. The role of intermittent inhibition in SDB will be studied in chronically instrumented, freely moving dogs. The central mechanisms producing intermittent inhibition associated with phasic events such as eye movements will be examined by dissecting the relationship between the startle response and phasic events. A link between the startle and phasic events has been proposed because spontaneous and evoked neurophysiological events during REMS are similar to events evoked by startling stimuli. In chronically instrumented dogs, we will experimentally alter the startle response and then measure the degree of intermittent inhibition during REMS, looking for a parallel or correlated change. We will also examine the development of respiratory muscle inhibition and startle responses in Bulldog pups and controls to determine whether an augmented startle response leads to the development of SDB. We will extend preliminary evidence that sleep deprivation and hypoxia augments startle- induced muscle inhibition during REMS. The result of augmented inhibition (SDB), would thus both reinforce the inhibition and produce a vicious cycle. The proposed studies will also attempt to relieve SDB by intervening, for the first time, in a discrete anatomical region of the CNS. The pathway mediating muscle inhibition during REMS is localized bilaterally in a small region of the pontine tegmentum. Lesions in this area can abolish muscle inhibition and, we propose, relieve SDB by increasing the drive for respiratory muscles during REMS. Finally, we will begin to study, for the first time, the neurochemical changes accompanying SDB studying the pontine region of the Bulldogs and control dogs with quantitative densometry and autoradiography to both localize and quantify specific neurotransmitters. These studies should provide important information relating to the progression, pathophysiology and neurochemistry of SDB.