TRANSMITTER RELEASE ONTO AIRWAY MOTONEURONS DURING SLEEP

睡眠期间向气道运动神经元释放发射器

• 批准号: 6505107
• 负责人: JEROME M SIEGEL
• 金额: $ 26.66万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6505107
• 关键词: REM sleep; cats; decerebration; gamma aminobutyrate; glycine; microdialysis; motor neurons; muscle tone; nasopharynx; neuroregulation; neurotransmitter transport; neurotransmitters; norepinephrine; periaqueductal gray matter; preoptic areas; respiratory muscles; serotonin; sleep; sleep apnea

Obstructive sleep apnea results from the interaction of an inadequate airway with the loss of tone in airway dilators. We hypothesize that the loss of tone during sleep is due to both: 1. Active inhibition of airway dilator motoneurons by glycine and GABA and 2. Disfacilitation of airway dilator motoneurons by the withdrawal of noradrenergic, serotonergic and glutamatergic inputs. We further hypothesize that this combination of inhibition and disfacilitation is present if trigeminal, hypoglossal and ambiguus motoneurons. We hypothesize that glutamate release onto trigeminal, hypoglossal and ambiguus motoneurons is selectively decreased in NREM sleep, whereas norepinephrine and serotonin released are minimal in REM sleep. We propose to test these hypothesis by conducting the first microdialysis studies of amino acid and norepinephrine release into motoneurons as a function of sleep state. We will also measure serotonin release in all these sites across the sleep cycle. We will study the release of these transmitters in the decerebrate animal and during naturally occurring sleep. We will determine if the profile of transmitter release across the sleep cycle differs in trigeminal, hypoglossal and ambiguus motoneurons. We will determine the effect of activating hypnogenic neurons in the preoptic area by local warming and the effect of inactivating periaqueductal gray neurons, on transmitter release onto upper airway dilator motoneurons. Our pilot data have already provided important new insights into how airway muscle tone is controlled and demonstrate the feasibility of our approach. This work will allow us to identify the major amino acid and monoamine neurotransmitters involved in the loss of tone in airway dilators during REM and NREM sleep. It will also have implications for understanding brain mechanisms controlling muscle tone in normal and pathological conditions.

梗阻性睡眠呼吸暂停是由一个不充分的相互作用造成的