TRANSMITTER RELEASE ONTO AIRWAY MOTONEURONS DURING SLEEP

阻塞性睡眠呼吸暂停是由不充分的 气道扩张器张力丧失。我们假设 睡眠时失去张力是由于以下两个原因：1.主动抑制呼吸道 甘氨酸和GABA对扩张器运动神经元的作用及2.呼吸道障碍 去甲肾上腺素能、5-羟色胺能和去甲肾上腺素能引起的运动神经元扩张 谷氨酸能输入。我们进一步假设，这一组合 如果三叉神经、舌下神经和 歧义运动神经元。我们假设谷氨酸释放到 三叉神经、舌下神经和歧义运动神经元选择性减少 在NREM睡眠中，去甲肾上腺素和5-羟色胺的释放很少 在快速眼动睡眠中。我们建议通过进行第一个实验来检验这些假设 脑内氨基酸和去甲肾上腺素释放的微渗析研究 运动神经元作为睡眠状态的函数。我们还将测量血清素 在整个睡眠周期中，在所有这些部位释放。我们会研究 这些递质在去大脑动物体内的释放和在 自然睡眠自然发生的睡眠我们将确定发射机的配置文件是否 在睡眠周期中，三叉神经、舌下神经和 歧义运动神经元。我们将确定激活的效果 局部加温对视前区催眠神经元的影响 中脑导水管周围灰质神经元失活，递质释放到 上呼吸道扩张器运动神经元。我们的试点数据已经提供了 对如何控制呼吸道肌肉张力和 论证了我们方法的可行性。 这项工作将使我们能够确定主要的氨基酸和单胺 参与呼吸道扩张器张力丧失的神经递质 REM和NREM睡眠。这也将对理解大脑产生影响。 在正常和病理条件下控制肌肉张力的机制。

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.