Respiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus-preBotzinger Complex Circuit
Respiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus-preBotzinger Complex Circuit
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DOI：
10.1007/s12264-020-00519-1
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发表时间：
2020-05-28
影响因子：
5.6
通讯作者：
Wang, Sheng
中科院分区：
文献类型：
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作者：
Liu, Na;Fu, Congrui;Wang, Sheng
蓝斑核（LC）与呼吸控制有关。先天性中枢性低通气综合征由在蓝斑核神经元中表达的配对样同源盒2b（Phox2b）基因突变所致。本研究旨在探讨对表达Phox2b的蓝斑核（Phox2b⁽ᴸᶜ⁾）神经元的刺激是否会影响呼吸，并揭示潜在的神经回路机制。将编码与Gq蛋白偶联的人M3毒蕈碱受体（hM3Dq）且依赖Cre重组酶的病毒载体导入Phox2b-Cre小鼠的蓝斑核。在通过体积描记法测量呼吸功能的同时，对转导了hM3Dq的神经元进行药理学激活。我们证实，对Phox2b⁽ᴸᶜ⁾神经元的选择性刺激可显著增加清醒小鼠的基础通气量。对这些神经元进行基因剔除会明显损害高碳酸血症通气反应。此外，刺激Phox2b⁽ᴸᶜ⁾神经元可增强前包钦格复合体神经元的活性。最后，Phox2b⁽ᴸᶜ⁾神经元的轴突投射到前包钦格复合体。综上所述，Phox2b⁽ᴸᶜ⁾神经元很可能通过蓝斑核 - 前包钦格复合体神经回路参与呼吸控制。
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 preBotzinger complex neurons. Finally, axons of Phox2b(LC)neurons projected to the preBotzinger complex. Collectively, Phox2b(LC)neurons contribute to the control of breathing most likelyviaan LC-preBotzinger complex circuit.