A top-down slow breathing circuit that alleviates negative affect in mice

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.