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Respiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus–preBötzinger Complex Circuit

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Abstract

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 (Phox2bLC) 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 Phox2bLC neurons significantly increased basal ventilation in conscious mice. Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses. Moreover, stimulation of Phox2bLC neurons enhanced the activity of preBötzinger complex neurons. Finally, axons of Phox2bLC neurons projected to the preBötzinger complex. Collectively, Phox2bLC neurons contribute to the control of breathing most likely via an LC–preBötzinger complex circuit.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31971058 and 31571174), and the Youth Fund for Scientific and Technological Research in Higher Education Institutions of Hebei Province (QN2019019) and the Youth Science and Technology Talent Support Program of Natural Science in Hebei Medical University (CYQD201907).

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  1. Na Liu, Congrui Fu and Hongxiao Yu have contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, China

    Na Liu, Hongxiao Yu, Yakun Wang, Luo Shi, Yinchao Hao, Fang Yuan & Sheng Wang

  2. Department of Physiology, Cangzhou Medical College, Cangzhou, 061000, China

    Na Liu

  3. School of Nursing, Hebei Medical University, Shijiazhuang, 050000, China

    Congrui Fu

  4. Hebei Key laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, China

    Xiangjian Zhang

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  1. Na Liu
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Correspondence to Sheng Wang.

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Liu, N., Fu, C., Yu, H. et al. Respiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus–preBötzinger Complex Circuit. Neurosci. Bull. 37, 31–44 (2021). https://doi.org/10.1007/s12264-020-00519-1

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  • DOI: https://doi.org/10.1007/s12264-020-00519-1

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