The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBel^CGRP neurons caused wakefulness, whereas optogenetic inhibition of PBel^CGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBel^CGRP terminals identified a network of forebrain sites under the control of a PBel^CGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea. VIDEO ABSTRACT.

中文翻译：

---

高碳酸血症期间睡眠引起的唤醒的遗传定义电路。

尚不清楚在睡眠呼吸暂停期间介导唤醒的精确神经回路。我们以前发现，外侧臂外侧臂旁核（PBel）中的谷氨酸能神经元在引起二氧化碳升高或缺氧中起关键作用。因为许多响应CO2的PBel神经元表达降钙素基因相关肽（CGRP），所以我们假设CGRP可能提供了CO2唤醒回路的分子标识符。在这里，我们报道PBel ^CGRP神经元的选择性化学发生和光遗传学激活引起清醒，而PBel ^CGRP神经元的光遗传学抑制阻止了对CO2的唤醒，但对声调或震动没有引起唤醒。PBel ^CGRP的光遗传抑制终端在PBel ^CGRP开关的控制下确定了一个前脑部位网络，这对于唤醒高碳酸血症的动物是必不可少的。我们的发现确定了一种新型的细胞靶标，可用于干预措施，以预防睡眠障碍以及阻塞性睡眠呼吸暂停伴随的心血管和认知后果。视频摘要。