Quantification of the State-Dependent Inputs to Hypoglossal Motoneurons

舌下运动神经元状态相关输入的量化

基本信息

批准号：
7924677
负责人：
Victor Borisovich Fenik
金额：
$ 24.04万
依托单位：
WEBSCIENCES INTERNATIONAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924677
关键词：
Adrenergic Agents Adult Affect Amino Acids Animal Model Apnea Behavior Disorders Carbachol Carbon Dioxide Cell Nucleus Chronic Complex Congestive Heart Failure Consensus Coronary Arteriosclerosis Data Development Diabetes Mellitus Disease Excessive Daytime Sleepiness Felis catus Glycine Hemoglobin Horns Hypertension Hypoglossal nerve structure Individual Injection of therapeutic agent Knowledge Measures Mediating Membrane Membrane Potentials Mental Depression Microdialysis Modeling Motor Neurons Movement Muscle Muscle Tonus Nature Nerve Neurotransmitters Norepinephrine Obstructive Sleep Apnea Operative Surgical Procedures Oral Oxygen Paralysed Pathology Patients Pharmaceutical Preparations Pharmacological Treatment Phase Play Population Quality of life REM Sleep Rattus Recurrence Relative (related person)Research Resistance Role Serotonin Site Sleep Sleep Deprivation Sleep Wake Cycle Soft Palate Spinal Stroke Strychnine System Testing Therapeutic Tongue Violence Wakefulness Woman adrenergic airway obstruction experience gamma-Aminobutyric Acid men neurochemistry noradrenergic orofacial postsynaptic pressure prevent public health relevance rapid eye movement receptor respiratory tongue root

项目摘要

DESCRIPTION (provided by applicant): Obstructive Sleep Apnea (OSA) affects about 4% of men and 2% of women of adult population. It is caused by partial or complete airway obstruction in individuals with anatomically compromised airways due to a decrease in upper airway muscle (including genioglossus muscle innervated by hypoglossal motoneurons) tone during sleep and especially during its rapid eye movement (REM) phase. The resulting hypopnea/apnea episodes cause recurrent decreases in hemoglobin oxygen saturation, accumulation of CO2, and frequent awakenings which results in chronic sleep deprivation and fragmentation. OSA patients suffer from excessive daytime sleepiness and diminished quality of life. OSA is also associated with hypertension, diabetes, coronary artery disease, strokes, and congestive heart failure. A large body of evidence suggests that two major state-dependent inputs control hypoglossal motoneurons: postsynaptic inhibition and aminergic disfacilitation. However, despite decades of research, there is no consensus about the mechanisms of the depression of this motoneuronal pool during REM sleep. In order to understand the responsible mechanisms, we will use intracellular recording during natural sleep and wakefulness. The following Specific Aims will be conducted: (1) to determine the contribution of postsynaptic inhibition mediated by inhibitory amino-acids to the depression of hypoglossal motoneuron activity during REM sleep and (2) to determine the contribution of aminergic disfacilitation to the REM sleep-related depression in the activity of hypoglossal motoneurons. We will obtain quantitative data regarding the contribution of these two major neurotransmitter systems in the depression of activity of hypoglossal motoneurons during REM sleep. This knowledge will advance our understanding of the mechanisms of state-dependent control of excitability of these motoneurons which could be used to develop effective pharmacological therapeutics to treat OSA. PUBLIC HEALTH RELEVANCE Obstructive Sleep Apnea (OSA) is caused by pathologies in the atonia of upper airway muscles during REM sleep. Accordingly, we will determine the relative contributions of the major state-dependent inputs that control hypoglossal motoneurons to advance our understanding of the mechanisms responsible for the atonia of muscles that are innervated by the hypoglossal nerve. This knowledge is a prerequisite for developing effective pharmacological treatments for OSA.

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）影响约4％的男性和2％的成人妇女。它是由于上空肌肉的下降肌肉（包括由降压运动神经元所支配的Genioglossus肌肉）在睡眠过程中，尤其是在快速眼动（REM）阶段的过程中，这是由于上呼吸道肌肉的减少（包括由降压运动神经元支配的Genioglossus肌肉）引起的。所得的呼吸症/呼吸暂停发作导致血红蛋白氧饱和度，二氧化碳的积累以及频繁觉醒的复发降低，从而导致长期睡眠剥夺和碎片化。 OSA患者白天嗜睡过多，生活质量降低。 OSA还与高血压，糖尿病，冠状动脉疾病，中风和充血性心力衰竭有关。大量证据表明，两个主要国家依赖性投入控制降压运动神经元：突触后抑制和氨基抗疾病。但是，尽管进行了数十年的研究，但在REM睡眠期间，该运动神经元池的抑郁症的机制尚无共识。为了了解负责任的机制，我们将在自然睡眠和清醒期间使用细胞内记录。将进行以下具体目的：（1）确定抑制性氨基酸介导的突触后抑制作用对REM睡眠期间降压性氨基酸酸性抑制作用以及（2）确定氨基抗溶液对REM睡眠相关抑郁症的抑制作用的贡献。我们将获得有关这两个主要神经递质系统在REM睡眠期间降压运动神经元活动抑制抑郁症中的贡献的定量数据。这些知识将促进我们对这些运动神经元兴奋性控制的机制的理解，这些机制可用于开发有效的药理治疗剂来治疗OSA。公共卫生相关性阻塞性睡眠呼吸暂停（OSA）是由REM睡眠期间上呼吸道肌肉的亚顿尼亚的病理引起的。因此，我们将确定控制降压运动神经元的主要状态依赖性输入的相对贡献，以促进我们对负责降低神经支配的肌肉肌肉的原理的理解。这些知识是开发有效的OSA药理治疗方法的先决条件。