INTRACELLULAR ANALYSIS OF AIRWAY MOTONEURONS DURING SLEEP

阻塞性睡眠呼吸暂停的临床体征反映在异常上 上呼吸道运动控制的模式。这些控制模式是 呼吸道通畅性的变化就是证据，这取决于 支配呼吸道肌肉系统的细胞的活动，尤其是 舌下运动神经元和歧义运动神经元。建议的目标是 研究是生成与电路有关的基本数据， 神经递质和神经调节剂负责控制这些 运动神经元。 细胞内的记录将从舌下和歧义获得 运动神经元；细胞外记录将由 提供单突触抑制的延髓运动抑制区 这些运动神经元的输入。电刺激将应用于 脑桥(脑桥口侧核)REM睡眠发生的部位 检查控制前面的兴奋性的电路 呼吸道通畅运动神经元。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 同时注射神经递质和神经调质拮抗剂 和激动剂并列在一起。这些研究将首先在#年进行。 一种动物睡眠模型，通过脑桥诱导失弛缓症 卡巴胆碱的微离子导入应用，以及随后在慢性 动物在自然睡眠和清醒过程中。 我们建议的研究的意义基于以下几点 各种因素。首先，为了了解和治疗阻塞性睡眠呼吸暂停， 有必要弄清控制人类活动的机制 呼吸道通畅运动神经元。其次，只有通过细胞内记录才能 区分突触后和突触后这两个基本过程 突触前，这可以促进运动神经元活动的减少 睡吧。为了准备这个应用程序，我们在细胞内记录 从舌下运动神经元中发现它们是突触后的 在快速眼动睡眠期间被抑制。这一发现是通过录音获得的 细胞内放置的微电极，与之前的数据相矛盾 通过间接方式获得的，但没有揭示存在 在这种状态下的突触后控制。因此，这些数据表明 目前所谓的呼吸道控制机制在 睡眠需要重新检查，并将与状态相关的数据定向- 必须发展对负责的运动神经元的独立控制。

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.