Rukhadze Irma, Carballo Nancy J, Bandaru Sathyajit S, Malhotra Atul, Fuller Patrick M, Fenik Victor B
Department of Veterans Affairs, Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
Department of Veterans Affairs, Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Respir Physiol Neurobiol. 2017 Oct;244:41-50. doi: 10.1016/j.resp.2017.07.001. Epub 2017 Jul 12.
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons. Administration of the hM4Di ligand, clozapine-N-oxide (CNO), in these mice decreased GG muscle activity during NREM sleep (F=17.1, p<0.05); a similar non-significant decrease was observed during wakefulness. CNO administration had no effect on neck muscle activity, respiratory parameters or state durations. In addition, CNO-induced inhibition of A1/C1 neurons did not alter the magnitude of the naturally occurring depression of GG activity during transitions from wakefulness to NREM sleep. These findings suggest that A1/C1 neurons have a net excitatory effect on GG activity that is most likely mediated by hypoglossal motoneurons. However, the activity of A1/C1 neurons does not appear to contribute to NREM sleep-related inhibition of GG muscle activity, suggesting that A1/C1 neurons regulate upper airway patency in a state-independent manner.
阻塞性睡眠呼吸暂停是一种常见的与睡眠相关的呼吸障碍，其神经机制尚未完全明确。舌下运动神经元为颏舌肌（GG）（一种主要的上呼吸道扩张肌）提供紧张性和吸气性激活，它接受来自延髓A1/C1神经元的儿茶酚胺能输入。我们旨在确定A1/C1神经元在睡眠和清醒期间对GG肌肉控制中的作用。为此，我们将病毒载体注射到DBH-cre小鼠体内，以在A1/C1神经元中选择性表达hMD4i抑制性化学感受器。在这些小鼠中给予hM4Di配体氯氮平N-氧化物（CNO）可降低非快速眼动睡眠期间的GG肌肉活动（F=17.1，p<0.05）；清醒期间观察到类似的但不显著的降低。给予CNO对颈部肌肉活动、呼吸参数或状态持续时间没有影响。此外，CNO诱导的对A1/C1神经元的抑制并没有改变从清醒到非快速眼动睡眠过渡期间GG活动自然发生的抑制幅度。这些发现表明，A1/C1神经元对GG活动具有净兴奋性作用，最有可能由舌下运动神经元介导。然而，A1/C1神经元的活动似乎并不导致与非快速眼动睡眠相关的GG肌肉活动抑制，这表明A1/C1神经元以与状态无关的方式调节上呼吸道通畅性。
