Jhang Jinho, Park Seahyung, Liu Shijia, O'Keefe David D, Han Sung
Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Department of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
Nat Neurosci. 2024 Dec;27(12):2455-2465. doi: 10.1038/s41593-024-01799-w. Epub 2024 Nov 19.
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), 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→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→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进行的，但行为和情绪对其的调节表明，皮质会向脑干呼吸网络输入信号，然而迄今为止，对该网络的特征描述甚少。在此，我们在小鼠中确定了一条从背侧前扣带回皮质（dACC）神经元到脑桥网状核GABA能抑制性神经元（PnC）的自上而下的呼吸通路，PnC随后投射到延髓腹外侧（VLM）。dACC→PnC活动与缓慢呼吸周期及随意性口面部行为相关，并受焦虑诱发条件的影响。对dACC→PnC→VLM回路进行光遗传学刺激可同时减缓呼吸并抑制焦虑样行为，而光遗传学抑制则会提高呼吸频率和焦虑样行为。这些发现表明，dACC→PnC→VLM回路在协调缓慢呼吸和减轻负面影响方面具有关键作用。我们的研究阐明了呼吸自上而下控制的回路基础，该回路可影响情绪状态。
