文章基本信息

标题：A descending pathway emanating from the periaqueductal gray mediates the development of cough-like hypersensitivity
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作者：Zhe Chen ; Ming-Tong Lin ; Chen Zhan 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：1
页码：1-20
DOI：10.1016/j.isci.2021.103641
语种：English
出版社：Elsevier
摘要：SummaryChronic cough is a common refractory symptom of various respiratory diseases. However, the neural mechanisms that modulate the cough sensitivity and mediate chronic cough remain elusive. Here, we report that GABAergic neurons in the lateral/ventrolateral periaqueductal gray (l/vlPAG) suppress cough processing via a descending pathway. We found that l/vlPAG neurons are activated by coughing-like behaviors and that tussive agent-evoked coughing-like behaviors are impaired after activation of l/vlPAG neurons. In addition, we showed that l/vlPAG neurons form inhibitory synapses with the nucleus of the solitary tract (NTS) neurons. The synaptic strength of these inhibitory projections is weaker in cough hypersensitivity model mice than in naïve mice. Important, activation of l/vlPAG GABAergic neurons projecting to the NTS decreases coughing-like behaviors. In contrast, suppressing these neurons enhances cough sensitivity. These results support the notion that l/vlPAG GABAergic neurons play important roles in cough hypersensitivity and chronic cough through disinhibition of cough processing at the medullary level.Graphical abstractDisplay OmittedHighlights•GABAergic neurons in the l/vlPAG inhibit coughing-like behaviors•The l/vlPAG sends predominately inhibitory projections to the NTS•l/vlPAG GABAergic neurons modulate coughing-like behaviors via descending projections•l/vlPAG-NTS projections mediate cough hypersensitivity via disinhibitory mechanismsBiological sciences; Sensory neuroscience; Techniques in neuroscience