Open AccessRespiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus–preBötzinger Complex Circuit
Author(s) -
Na Liu,
Congrui Fu,
Huan Yu,
Yakun Wang,
Luo Shi,
Yinchao Hao,
Yuan Fang,
Xiangjian Zhang,
Sheng Wang
Publication year - 2020
Publication title -
neuroscience bulletin/neuroscience bulletin
Language(s) - English
Resource type - Journals
eISSN - 1673-7067
pISSN - 1995-8218
DOI - 10.1007/s12264-020-00519-1
Subject(s) - locus coeruleus , stimulation , biology , neuroscience , respiratory center , respiratory system , central nervous system , anatomy
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.