A descending pathway emanating from the periaqueductal gray mediates the development of cough-like hypersensitivity.
A descending pathway emanating from the periaqueductal gray mediates the development of cough-like hypersensitivity.
复制标题
从导水管周围灰质发出的下行通路介导咳嗽样超敏反应的发生
DOI：
10.1016/j.isci.2021.103641
复制
发表时间：
2022-01-21
期刊：
影响因子：
5.8
通讯作者：
Liu MJ
中科院分区：
文献类型：
--
作者：
Chen Z;Lin MT;Zhan C;Zhong NS;Mu D;Lai KF;Liu MJ
慢性咳嗽是多种呼吸道疾病常见的难治性症状。然而，调节咳嗽敏感性和介导慢性咳嗽的神经机制仍然难以捉摸。在这里，我们报告，GABA能神经元在外侧/腹外侧的导水管周围灰质（l/vlPAG）抑制咳嗽处理通过下行通路。我们发现，l/vlPAG神经元激活咳嗽样行为和咳嗽剂诱发的咳嗽样行为受损后，l/vlPAG神经元的激活。此外，我们发现，l/vlPAG神经元与孤束核（NTS）神经元形成抑制性突触。这些抑制性投射的突触强度在咳嗽超敏反应模型小鼠中比在幼稚小鼠中弱。重要的是，投射到NTS的l/vlPAG GABA能神经元的激活减少了咳嗽样行为。相反，抑制这些神经元会增强咳嗽敏感性。这些结果支持了这样的观点，即l/vlPAG GABA能神经元通过在延髓水平解除对咳嗽处理的抑制而在咳嗽超敏性和慢性咳嗽中起重要作用。l/vlPAG中的GABA能神经元抑制咳嗽样行为l/vlPAG主要向NTS发送抑制性投射l/vlPAG GABA能神经元通过下行投射调节咳嗽样行为l/vlPAG-NTS投射通过去抑制机制介导咳嗽超敏反应生物科学;感觉神经科学;神经科学技术
Chronic 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. 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 mechanisms Biological sciences; Sensory neuroscience; Techniques in neuroscience
登录
查看更多内容
影响因子：
3.2
作者：
Lin RL;Gu Q;Khosravi M;Lee LY
通讯作者：
Lee LY
DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
DOI：
10.1186/1745-9974-3-5
发表时间：
2007-03-23
期刊：
Cough (London, England)
影响因子：
--
作者：
Everett CF;Kastelik JA;Thompson RH;Morice AH
通讯作者：
Morice AH
影响因子：
3.2
作者：
Bolser，DC
通讯作者：
Bolser，DC
影响因子：
18.2
作者：
Koch SC;Acton D;Goulding M
通讯作者：
Goulding M