INTRACELLULAR ANALYSIS OF AIRWAY MOTONEURONS DURING SLEEP

睡眠期间气道运动神经元的细胞内分析

• 批准号: 6202630
• 负责人: MICHAEL H CHASE
• 金额: $ 23.08万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202630
• 关键词: cats; electrostimulus; motor neurons; muscle tone; neural transmission; neurochemistry; neurophysiology; neuroregulation; nontherapeutic iontophoresis; psychic activity level; respiratory muscles; single cell analysis; sleep apnea

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.

阻塞性睡眠呼吸暂停的临床症状表现为异常 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 支配气道肌肉组织的细胞的活动，特别是 舌下运动神经元和模糊运动神经元。拟议的目标 研究是生成与电路相关的基本数据， 负责控制这些的神经递质和神经调节剂 运动神经元。 细胞内记录将从舌下肌和模糊肌获得 运动神经元；细胞外记录将由神经元获得 提供单突触抑制的髓质运动抑制区 输入到这些运动神经元。电刺激将应用于 快速眼动睡眠发生的部位位于脑桥（口桥核） 检查控制前一神经元兴奋性的电路 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节剂拮抗剂 和细胞激动剂。这些研究将首先在 一种睡眠动物模型，其中通过脑桥诱导失张力 卡巴胆碱微离子电渗疗法的应用，以及随后在慢性病中的应用 动物在自然发生的睡眠和清醒状态下。 我们提出的研究的意义基于以下几点 因素。首先，为了了解和治疗阻塞性睡眠呼吸暂停， 有必要澄清控制其活动的机制 气道通畅运动神经元。其次，只有通过细胞内记录才能 区分突触后和突触这两个基本过程 突触前，可以促进运动神经元活动的减少 睡觉。为了准备这个应用，我们记录了细胞内 来自舌下运动神经元，发现它们位于突触后 在快速眼动睡眠期间受到抑制。这一发现是通过记录获得的 使用细胞内放置的微电极，与之前的数据相矛盾 通过间接手段获得，但未揭示 该状态期间的突触后控制。因此，这些数据表明 目前声称的气道控制机制在 需要重新检查睡眠和与状态相关的直接数据 必须发展负责运动神经元的依赖性控制。