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一个用于控制呼吸稳态的分子定义的髓质网络。

A Molecularly Defined Medullary Network for Control of Respiratory Homeostasis.

作者信息

Deng Tianjiao, Jing Xinyi, Shao Liuqi, Wang Yakun, Fu Congrui, Yu Hongxiao, Wang Xiaoyi, Zhao Xue, Kong Fanrao, Ji Yake, Tian Xiaochen, He Wei, Bi Shangyu, Shi Luo, Wang Hanqiao, Yuan Fang, Wang Sheng

机构信息

Department of Neurobiology, Hebei Medical University, Shijiazhuang, 050017, China.

Department of Sleep Medicine, Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.

出版信息

Adv Sci (Weinh). 2025 May;12(18):e2412822. doi: 10.1002/advs.202412822. Epub 2025 Mar 16.

DOI:10.1002/advs.202412822
PMID:40089863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12079440/
Abstract

The dynamic interaction between central respiratory chemoreceptors and the respiratory central pattern generator constitutes a critical homeostatic axis for stabilizing breathing rhythm and pattern, yet its circuit-level organization remains poorly characterized. Here, the functional connectivity between two key medullary hubs: the nucleus tractus solitarius (NTS) and the preBötzinger complex (preBötC) are systematically investigated. These findings delineate a medullary network primarily comprising Phox2b-expressing NTS neurons (NTS), GABAergic NTS neurons (NTS), and somatostatin (SST)-expressing preBötC neurons (preBötC). Photostimulation of NTS neurons projecting to the preBötC potently amplifies baseline ventilation, whereas genetic ablation of these neurons or knockout of their transient receptor potential channel 5 (TRPC5) significantly blunts the CO-stimulated ventilatory responses. Conversely, NTS neuron stimulation inhibits or halts breathing partially via monosynaptic inhibition of NTS neurons projecting to the preBötC. Additionally, photostimulation of preBötC neurons projecting to the NTS drives deep and slow breathing through coordinated modulation of NTS and NTS neurons. These findings collectively identify an important medullary network that integrates chemosensory feedback with respiratory motor output, enabling dynamic tuning of breathing patterns to metabolic demands.

摘要

中枢呼吸化学感受器与呼吸中枢模式发生器之间的动态相互作用构成了稳定呼吸节律和模式的关键稳态轴，但其在回路水平的组织特征仍不清楚。在此，系统研究了延髓两个关键中枢之间的功能连接：孤束核（NTS）和前包钦格复合体（preBötC）。这些发现描绘了一个主要由表达Phox2b的NTS神经元（NTS）、GABA能NTS神经元（NTS）和表达生长抑素（SST）的preBötC神经元（preBötC）组成的延髓网络。光刺激投射到preBötC的NTS神经元可显著增强基线通气，而这些神经元的基因消融或其瞬时受体电位通道5（TRPC5）的敲除则显著减弱CO刺激的通气反应。相反，刺激NTS神经元可通过对投射到preBötC的NTS神经元的单突触抑制部分抑制或停止呼吸。此外，光刺激投射到NTS的preBötC神经元通过对NTS和NTS神经元的协同调节驱动深呼吸和慢呼吸。这些发现共同确定了一个重要的延髓网络，该网络将化学感受反馈与呼吸运动输出整合在一起，能够根据代谢需求动态调整呼吸模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/6b032390fd97/ADVS-12-2412822-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/68ce8ebb0404/ADVS-12-2412822-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/85af34697cc9/ADVS-12-2412822-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/2897c76178b9/ADVS-12-2412822-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/53490b8ad387/ADVS-12-2412822-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/bfb15748216c/ADVS-12-2412822-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/8f7f0eac3f2f/ADVS-12-2412822-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/30a2d4e5d7c6/ADVS-12-2412822-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/1e3033a8e083/ADVS-12-2412822-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/6b032390fd97/ADVS-12-2412822-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/68ce8ebb0404/ADVS-12-2412822-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/85af34697cc9/ADVS-12-2412822-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/2897c76178b9/ADVS-12-2412822-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/53490b8ad387/ADVS-12-2412822-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/bfb15748216c/ADVS-12-2412822-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/8f7f0eac3f2f/ADVS-12-2412822-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/30a2d4e5d7c6/ADVS-12-2412822-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/1e3033a8e083/ADVS-12-2412822-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a868/12079440/6b032390fd97/ADVS-12-2412822-g001.jpg

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本文引用的文献

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Activation of Centromedial Amygdala GABAergic Neurons Produces Hypotension in Mice.中央内侧杏仁核GABA能神经元的激活会导致小鼠血压降低。
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Whole-brain inputs and outputs of Phox2b and GABAergic neurons in the nucleus tractus solitarii.
孤束核中Phox2b和GABA能神经元的全脑输入与输出
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Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex.吸气和叹息呼吸节律依赖于 PreBötzinger 复合体中不同的细胞信号机制。
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Effect of breathing exercises on blood pressure and heart rate: A systematic review and meta-analysis.呼吸练习对血压和心率的影响：一项系统评价与荟萃分析
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The astrocytic Na -HCO cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.星形胶质细胞的 Na+-HCO3-共转运体 NBCe1 对于呼吸化学敏感性不是必需的。
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CaMKIIα Promoter-Controlled Circuit Manipulations Target Both Pyramidal Cells and Inhibitory Interneurons in Cortical Networks.CaMKIIα 启动子控制的电路操作靶向皮质网络中的锥体神经元和抑制性中间神经元。
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