The locus coeruleus (LC) has been implicated in the control of breathing. Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2b (Phox2b) gene that is expressed in LC neurons. The present study was designed to address whether stimulation of Phox2b-expressing LC (Phox2b^LC) neurons affects breathing and to reveal the putative circuit mechanism. A Cre-dependent viral vector encoding a Gq-coupled human M3 muscarinic receptor (hM3Dq) was delivered into the LC of Phox2b-Cre mice. The hM3Dq-transduced neurons were pharmacologically activated while respiratory function was measured by plethysmography. We demonstrated that selective stimulation of Phox2b^LC neurons significantly increased basal ventilation in conscious mice. Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses. Moreover, stimulation of Phox2b^LC neurons enhanced the activity of preBötzinger complex neurons. Finally, axons of Phox2b^LC neurons projected to the preBötzinger complex. Collectively, Phox2b^LC neurons contribute to the control of breathing most likely via an LC–preBötzinger complex circuit.

蓝斑（LC）与呼吸控制有关。先天性中枢性低通气综合征是由在 LC 神经元中表达的配对同源框 2b (Phox2b) 基因突变引起的。本研究旨在解决刺激表达 Phox2b 的 LC (Phox2b ^LC ) 神经元是否会影响呼吸并揭示推定的回路机制。将编码 Gq 偶联的人 M3 毒蕈碱受体 (hM3Dq) 的 Cre 依赖性病毒载体递送到 Phox2b-Cre 小鼠的 LC 中。hM3Dq 转导的神经元被药理学激活，而呼吸功能通过体积描记法测量。我们证明了对 Phox2b ^{LC的选择性刺激}神经元显着增加了清醒小鼠的基础通气量。这些神经元的基因消融显着损害了高碳酸血症通气反应。此外，Phox2b ^LC神经元的刺激增强了 preBötzinger 复合神经元的活性。最后，Phox2b ^LC神经元的轴突投射到 preBötzinger 复合体。总的来说，Phox2b ^{LC神经元最有可能}通过LC-preBötzinger 复杂电路有助于控制呼吸。