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 PBelCGRPneurons caused wakefulness, whereas optogenetic inhibition of PBelCGRPneurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBelCGRPterminals identified a network of forebrain sites under the control of a PBelCGRPswitch 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.

中文翻译：

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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，我们报告PBelCGRPneurons的选择性化学发生和光遗传学激活引起清醒，而PBelCGRPneurons的光遗传学抑制阻止了对CO2的唤醒，但并未引起声音或震动。对PBelCGRP末端的光遗传学抑制在PBelCGRP开关的控制下确定了前脑位点的网络，这是引起高碳酸血症动物所必需的。