STATE-DEPENDENT MODULATION OF RESPIRATORY MOTONEURONS

睡眠时反复阻塞呼吸道，导致睡眠呼吸暂停和 伴随低氧血症，影响2-5%的成年人口。这个 梗阻最常见于口咽部，被认为是 由解剖异常与上颌骨功能不全共同作用 在睡眠期间适当地激活呼吸道肌肉。频率和频率 呼吸暂停的严重程度通常在REM睡眠期间最严重，当 许多呼吸道肌肉的低张力与全身性 体位性肌肉张力。这一点，加上间歇性和 呼吸暂停的不均匀性质，表明中枢神经控制是一种 这是该综合征的重要组成部分，但其机制尚不清楚。而当 颧舌肌通常被认为是最重要的 控制口咽通畅的肌肉，咽部的其他肌肉 墙壁和上颚可能同等(或更重要)地允许 发生阻碍。研究紧张症的神经机制 在睡眠中，一种急性动物模型的上呼吸道肌肉 肌肉紧张症形成的肌肉紧张症与紧张症直接对应 的快速眼动睡眠可以通过药物产生，通过注射 胆碱能激动剂卡巴胆碱进入脑桥，允许解剖 潜在的机制。该模型的应用表明，该模型能较好地控制上、下部运动。 呼吸道肌肉与姿势肌肉的不同之处在于 障碍(消除兴奋)起主导作用，而不是 突触抑制。这导致了目前的普遍假设 去易化作用对大鼠脑内胺能神经元的兴奋作用 快速眼动睡眠中的脑干导致上呼吸道张力。此外，它还 假设由于运动神经元膜的不同 受体，这种非易化会导致咽部肌肉活动 比喉部肌肉活动受到更强的抑制。品种繁多 补充生理学和药理学技术 (微电极记录、微注射、微离子导入、 微透析)将被用来测试各种 中缝尾部胺能神经元分泌的神经递质 (5-羟色胺、促甲状腺激素释放激素、P物质)和基因座 蓝斑复合体(去甲肾上腺素)及其特异性受体激动剂 和拮抗剂，对运动神经元对不同上皮层兴奋性的影响 呼吸道肌肉。咽部、喉部、舌部和腭部的运动神经元 我们将对肌肉进行研究。将特别注意质量 和/或数量上的差异来维持 不同上呼吸道运动神经元组的活动度。结果是 该项目应能更好地了解这些机制。 睡眠中潜在的上呼吸道张力和药理学指导 预防和治疗呼吸道疾病的方法(尚不适用) 睡眠时的闭塞。

Repetitive airway occlusion during sleep, resulting in sleep apnea and concomitant hypoxemia, affects 2-5% of the adult population. The obstruction is most common in the oropharynx and is considered to result from anatomic abnormalities acting in concert with a failure of upper airway muscles to be properly activated during sleep. The frequency and severity of the apneas is often greatest during REM sleep, when a hypotonia of many airway muscles occurs in parallel with a generalized postural muscle atonia. This, together with the intermittent and nonuniform nature of the apneas, points to central nervous control as an important component of the syndrome, but the mechanisms are unknown. While the genioglossus muscle is often considered to be the most important muscle governing oropharyngeal patency, other muscles of the pharyngeal wall and palate may be equally (or more) important in allowing the obstruction to occur. To study the neural mechanisms underlying the atonia of upper airway muscles during sleep, an acute animal model has been developed whereby a muscle atonia that directly corresponds to the atonia of REM sleep can be produced pharmacologically, by injecting the cholinergic agonist carbachol into the pons, allowing dissection of the underlying mechanisms. Use of this model showed that the control of upper airway muscles differs from that of postural muscles in that disfacilitation (removal of excitation) plays the dominant role, not synaptic inhibition. This led to the current general hypothesis that disfacilitation from the excitatory effects of the aminergic neurons of the brainstem during REM sleep leads to upper airway atonia. Further, it is hypothesized that, due to differences in motoneuronal membrane receptors, this disfacilitation will lead to pharyngeal muscle activity being more strongly suppressed than laryngeal muscle activity. A variety of complementary physiological and pharmacological techniques (microelectrode recording, microinjection, microiontophoresis, microdialysis) will be used to test the effects of various neurotransmitters secreted by the aminergic neurons of the caudal raphe (serotonin, thyrotropin releasing hormone, substance P) and locus coeruleus complex (noradrenaline), and their specific receptor agonists and antagonists, on the excitability of motoneurons to different upper airway muscles. Motoneurons to pharyngeal, laryngeal, glossal and palatal muscles will be studied. Particular attention will be paid to qualitative and/or quantitative differences in the mechanisms of maintaining the activity in the different upper airway motoneuronal groups. The results of this project should provide a better understanding of the mechanisms underlying upper airway atonia during sleep and guide pharmacological approaches (not yet available) to the prevention and treatment of airway occlusions during sleep.