INTRACELLULAR ANALYSIS OF AIRWAY MOTONEURONS DURING SLEEP

阻塞性睡眠呼吸暂停综合征的临床表现是 上呼吸道运动控制模式。这些控制模式是 通过气道通畅性的变化来证明，这取决于 神经支配气道肌肉组织的细胞的活动，特别是 舌下神经和疑核运动神经元。建议的目标 研究是生成与电路相关的基本数据， 神经递质和神经调质负责控制这些 运动神经元 将从舌下神经和疑神经获得细胞内记录 运动神经元;细胞外记录将由运动神经元获得。 延髓运动抑制区提供单突触抑制 输入到这些运动神经元。电刺激将应用于 在脑桥中产生REM睡眠的部位（脑桥口核）， 检查控制前面的兴奋性的电路 气道通畅运动神经元。这些运动神经元的神经化学控制 将通过细胞内记录来确定，而 同时喷射神经递质和神经调质拮抗剂 和激动剂。这些研究将首先在 一种通过脑桥诱发肌张力不足的动物睡眠模型 卡巴胆碱的微离子电渗应用，随后在慢性 动物在自然发生的睡眠和觉醒。 我们提出的研究的意义是基于以下几点 因素首先，为了了解和治疗阻塞性睡眠呼吸暂停， 关键是要澄清控制活动的机制， 气道通畅运动神经元。第二，只有通过细胞内记录， 一个是区分两个基本过程，突触后和 突触前，可以促进运动神经元活动的减少， 睡吧为了准备这项应用，我们在细胞内记录了 从舌下神经运动神经元，并发现他们是突触后 在快速眼动睡眠期间被抑制。这一发现是通过记录 与细胞内放置的微电极相矛盾， 通过间接方式获得，没有显示存在 在这种状态下的突触后控制。因此，这些数据表明， 目前所声称的气道控制机制， 睡眠需要重新检查和直接数据有关的状态- 必须发展对负责任的运动神经元的依赖性控制。

The clinical signs of obstructive sleep apnea are reflected in abnormal patterns of upper airway motor control. These patterns of control are evidenced by changes in airway patency, which are dependent on the activity of cells that innervate the airway musculature, most specifically hypoglossal and ambiguus motoneurons. The objective of the proposed research is to generate basic data relating to the circuitry, neurotransmitters and neuromodulators responsible for the control of these motoneurons. Intracellular recordings will be obtained from hypoglossal and ambiguus motoneurons; extracellular recording will be obtained by neurons of the medullary motor inhibitory area that provide a monosynaptic inhibitory input to these motoneurons. Electrical stimulation will be applied to the site of REM sleep generation in the pons (the nucleus pontis oralis) to examine the circuitry that controls the excitability of the preceding airway patency motoneurons. The neurochemical control of these motoneurons will be determined by recording from them intracellularly, while simultaneously ejecting neurotransmitter and neuromodulator antagonists and agonists juxta-cellularly. These studies will first be undertaken in an animal model of sleep in which atonia is induced via the pontine microiontophoretic application of carbachol, and subsequently in chronic animals during naturally occurring sleep and wakefulness. The significance of our proposed studies is based upon the following factors. First, in order to understand and treat obstructive sleep apnea, it is essential to clarify the mechanisms that control the activity of airway patency motoneurons. Second, only by recording intracellularly can one differentiate between the two fundamental processes, postsynaptic and presynaptic, that can promote a decrease in motoneuron activity during sleep. In preparation for this application, we recorded intracellularly from hypoglossal motoneurons and found that they are postsynaptically inhibited during REM sleep. This finding, which was obtained by recording with intracellularly-placed microelectrodes, contradicts previous data obtained by indirect means which did not reveal the presence of postsynaptic control during this state. These data therefore suggest that the currently purported airway control mechanisms that operate during sleep need to be reexamined and direct data relating to the state- dependent control of the responsible motoneurons must be developed.