Activation of Phox2b-Expressing Neurons in the Nucleus Tractus Solitarii Drives Breathing in Mice

• DOI: 10.1523/jneurosci.2048-18.2018
• Publication Date: 2019-01-09T23:35:39Z
• Authors: Congrui Fu; Luo Shi; Ziqian Wei; Hongxiao Yu; Yinchao Hao; Yanming Tian; Yixian Liu; Yi Zhang; Xiangjian Zhang; Fang Yuan; Sheng Wang
• Keywords: Solitary nucleus

The nucleus tractus solitarii (NTS) is implicated in the control of breathing, but neuronal phenotype and circuit mechanism involved such a physiological function remain incompletely understood. This study focused on respiratory role paired-like homeobox 2b gene (Phox2b)-expressing NTS neurons sought to determine whether selective stimulation this set activates breathing male mice. A Cre-dependent vector encoding Gq-coupled human M3 muscarinic receptor (hM3Dq) was microinjected into Phox2b-Cre transgenic hM3Dq-transduced were pharmacologically activated conscious mice while effects measured by plethysmography. We demonstrate that chemogenetic Phox2b-expressing significantly increased baseline minute volume via an increase frequency rather than tidal volume. Chemogenetic also synergized with moderate CO 2 enhance pulmonary ventilatory response. Selective ablation notably attenuated hypercapnic Moreover, histological evidence revealed activity preBötzinger complex. Finally, we presented neuroanatomical direct projection putative central pattern generator. Overall, these findings suggest activation potentiates ventilation excitatory drive generator group required for SIGNIFICANCE STATEMENT has been breathing. (Phox2b) disease-defining congenital hypoventilation syndrome restrictively present brainstem nucleus, including NTS. Using approach, herein vigorously rodents. Genetic attenuates fraction exhibit sensitivity presumably as chemoreceptors. methodology expected provide future applicability patients sleep-related or apnea.