Single Motor Unit Genioglossus Recordings to Understand Sleep Apnea Pathogenesis

描述(申请人提供)：阻塞性睡眠呼吸暂停(OSA)是一种非常常见的疾病，对健康有重大影响。导致OSA的根本问题是那些具有解剖学倾向的人在睡眠期间对上呼吸道肌肉的神经控制失败。通过对上呼吸道扩张肌(如颧舌肌)进行多单位肌电记录，在了解阻塞性睡眠呼吸暂停的发病机制方面取得了一些进展。虽然这些研究有助于确定这些肌肉在保护上呼吸道通畅中的重要性，以及重要的潜在刺激，但我们对呼吸暂停的发病机制仍有相对粗略的了解。利用这一领域的较新技术，我们现在正在积极记录单个运动单位(SMU)，以确定对整个颧舌肌活动有贡献的各种部件的特征。我们描述了六种不同的颧舌肌放电SMU模式，其中一些主要在吸气时活动，一些在整个呼吸周期中持续活动，还有一些具有不同的组合。值得注意的是，从它们的活动角度来看，这些不同的SMU似乎具有不同的反应特征，例如从清醒到睡眠。同样，这些不同的SMU对标准呼吸刺激的反应似乎完全不同。具体地说，SMU在从清醒到睡眠的转变中行为的变化是基于先前清醒期间的放电模式。我们还观察到OSA患者的SMU与对照组和REM睡眠期间的主要差异。此外，某些类型的运动单位似乎与上呼吸道塌陷的发生密切相关。基于动物和人类的数据，我们正在开发一个有效的神经生物学模型，以了解调节GG活动的主要途径，以及这些途径如何在OSA中功能失调。因此，我们坚信SMU在正常受试者和OSA患者中的详细特征以及SMU行为如何从清醒到NREM和REM睡眠的变化将导致我们对呼吸暂停发病机制的理解取得重大进展。最终，这种上呼吸道运动控制工作模式的发展，以及OSA肌肉控制异常的特征，将有助于确定OSA治疗的治疗靶点。与公共卫生相关。阻塞性睡眠呼吸暂停是一种高度流行的、使人虚弱的疾病，对大脑和心血管系统的影响是公认的。目前对睡眠呼吸暂停发生的原因的了解还不完全，尽管对上呼吸道扩张肌的控制被认为是重要的，比如膝舌肌。单运动单位技术使科学家能够了解控制肌肉的各种不同的神经元组，并推断这些神经元是如何控制的；此类研究对于出现这种疾病的新治疗方法至关重要，例如睡眠呼吸暂停的药物治疗。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a very common disease with major health consequences. The fundamental problem leading to OSA is a failure of the neural control of the upper airway muscles during sleep in those anatomically predisposed. Some progress has been made in the understanding of the mechanisms underlying OSA by performing multi-unit electromyography recordings on upper airway dilator muscles such as the genioglossus (GG). Although these studies have been useful in establishing the importance of these muscles in protecting upper airway patency, and the potential stimuli of importance, we still have a relatively cursory understanding of apnea pathogenesis. Using a newer technique in this area, we are now actively recording single motor units (SMUs) in order to establish the characteristics of the various components contributing to overall genioglossus activity. We have characterized six different SMU patterns of genioglossus firing, some with activity predominantly during inspiration, some with constant activity throughout the respiratory cycle, and some with various combinations. Of note these various SMUs appear to have different response characteristics from standpoint of their activity, for example in going from wakefulness to sleep. Similarly, the response of these various SMUs to standard respiratory stimuli appears to be quite different. Specifically, the change in behavior of SMUs in the transitions from wakefulness to sleep is predicated on the discharge pattern during prior wakefulness. We have also observed major differences in SMUs in OSA patients compared to controls and during REM sleep. Also, certain types of motor units appear to be critically involved in the development of upper airway collapse. Based on animal and human data, we are in the process of developing a working neurobiological model to understand the major pathways regulating GG activity, and how these may be dysfunctional in OSA. We therefore strongly believe that the detailed characterization of SMUs in normal subjects and OSA patients and how SMU behavior changes from wakefulness to NREM and REM sleep will lead to major advances in our understanding of apnea pathogenesis. Ultimately, the development of this working model of upper airway motor control, and the characterization of the muscle control abnormalities in OSA will facilitate the identification of therapeutic targets for the treatment of OSA. PUBLIC HEALTH RELEVANCE. Obstructive sleep apnea is a highly prevalent and debilitating disease with well established consequences to the brain and cardiovascular system. Current understanding of why sleep apnea occurs is incomplete, although the control of upper airway dilator muscles such as the genioglossus are thought to be important. Single motor unit technology allows scientists to understand the various different groups of neurons that are controlling the muscle and to draw inferences regarding how these neurons are being controlled; such studies will be critical for new treatments for this condition to emerge, such as drug treatment of sleep apnea.