NEURAL INHIBITION AND REM SLEEP DISORDERED BREATHING

睡眠呼吸障碍（SDB）是一种广泛的、严重的疾病 以间歇性，重复性缺氧为特征， 睡吧 在大多数患者中，呼吸紊乱是最严重的 快速眼动睡眠（REMS） 我们会研究 英语快速眼动睡眠障碍的中枢神经机制 斗牛犬，谁有一个自然发生的，通常严重的形式 和对照犬（比格犬）。 基于先前 研究和初步数据，我们建议，间歇性 呼吸肌抑制在SDB中起重要作用 在REMS期间。 此外，异步抑制上 气道和平滑肌也可能导致阻塞 中枢性呼吸暂停 间歇性抑制在SDB中的作用 在长期使用器械、自由活动的犬中进行研究。 的 产生间歇性抑制的中枢机制 对于诸如眼球运动的阶段性事件， 剖析惊吓反应和 阶段性事件 惊吓和阶段性事件之间的联系 提出是因为自发的和诱发的神经生理学 在快速眼动睡眠中发生的事件与 刺激。 在长期仪器狗，我们将实验 改变惊吓反应， REMS期间的间歇性抑制，寻找平行或 相关的变化。 我们亦会研究 斗牛犬幼犬的呼吸肌抑制和惊吓反应 并控制以确定增强的惊吓反应是否 这就导致了SDB的发展。 我们将延长初步 睡眠不足和缺氧会增加惊吓的证据 在REMS期间引起肌肉抑制。 增强的结果 抑制（SDB），因此既会加强抑制， 形成恶性循环。 拟议的研究还将试图 第一次，通过干预一个离散的 CNS的解剖区域。 介导肌通路 REMS期间的抑制位于双侧的小区域， 脑桥被盖 这一区域的病变可使肌肉萎缩 抑制，我们建议，通过增加驱动器， 快速眼动睡眠时的呼吸肌 最后，我们将开始学习， 第一次，伴随SDB的神经化学变化 研究了斗牛犬和对照犬的脑桥区域， 定量密度测定和放射自显影， 量化特定的神经递质。 这些研究将提供 与进展相关的重要信息， SDB的病理生理学和神经化学。

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.