Although breathing is primarily automatic, its modulation by behavior and emotions suggests cortical inputs to brainstem respiratory networks, which hitherto have received little characterization. Here we identify in mice a top-down breathing pathway from dorsal anterior cingulate cortex (dACC) neurons to pontine reticular nucleus GABAergic inhibitory neurons (PnC^GABA), which then project to the ventrolateral medulla (VLM). dACC→PnC activity correlates with slow breathing cycles and volitional orofacial behaviors and is influenced by anxiogenic conditions. Optogenetic stimulation of the dACC→PnC^GABA→VLM circuit simultaneously slows breathing and suppresses anxiety-like behaviors, whereas optogenetic inhibition increases both breathing rate and anxiety-like behaviors. These findings suggest that the dACC→PnC^GABA→VLM circuit has a crucial role in coordinating slow breathing and reducing negative affect. Our study elucidates a circuit basis for top-down control of breathing, which can influence emotional states.

尽管呼吸主要是自动的，但它受行为和情绪的调节表明皮层输入到脑干呼吸网络，而迄今为止几乎没有得到表征。在这里，我们在小鼠中确定了从背侧前扣带皮层 （dACC） 神经元到脑桥网状核 GABA 能抑制神经元 （PnC^GABA） 的自上而下的呼吸通路，然后投射到腹外侧延髓 （VLM）。dACC→PnC 活性与缓慢的呼吸周期和自主口面部行为相关，并受焦虑条件的影响。dACC→PnC^GABA→VLM 回路的光遗传学刺激同时减慢呼吸并抑制焦虑样行为，而光遗传学抑制同时增加呼吸频率和焦虑样行为。这些发现表明，dACC→PnC^GABA→VLM 回路在协调缓慢呼吸和减少负面影响方面起着至关重要的作用。我们的研究阐明了自上而下控制呼吸的回路基础，这可以影响情绪状态。