Chemoreception and neuroplasticity in respiratory circuits.
Chemoreception and neuroplasticity in respiratory circuits.
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DOI：
10.1016/j.expneurol.2016.05.036
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发表时间：
2017-01
影响因子：
5.3
通讯作者：
Molkov, Yaroslav I.
中科院分区：
文献类型：
--
作者：
Barnett, William H.;Abdala, Ana P.;Paton, Julian F. R.;Rybak, Ilya A.;Zoccal, Daniel B.;Molkov, Yaroslav I.
关键词：
呼吸中枢模式发生器必须对化学感觉线索作出反应，以维持血液和组织中的氧气（O2）和二氧化碳（CO2）稳态。为此，位于外周和中枢神经系统中的感觉细胞监测O2和CO2的动脉分压，并在缺氧和高碳酸血症的条件下启动呼吸和自主反射调节。在慢性间歇性缺氧（CIH）条件下，由孤束核介导的重复外周化学感受器输入诱导呼吸回路的可塑性变化，改变基线呼吸和交感神经运动输出，并导致化学反射敏化，主动呼气和动脉高压。在此，我们探讨了CIH诱导的神经可塑性主要由前Bötzinger复合体中吸气前/吸气神经元兴奋性增加组成的可能性。为了评估这一假设并阐明CIH治疗动物中出现主动呼气和交感神经过度活跃的神经机制，我们扩展了之前开发的脑干呼吸交感神经网络计算模型，以重现CIH后外周和中枢化学反射的实验数据。该模型纳入了第二阶NTS神经元和外周化学感受器传入，呼吸模式发生器，和交感神经元之间的神经元连接在延髓头端腹外侧，以捕捉关键特征的交感神经和呼吸反应外周化学反射刺激。我们的模型确定了潜在的神经元组招募外周化学反射刺激，可能需要的发展吸气，呼气和交感神经反射反应。此外，我们的模型预测，在前Bötzinger复杂的吸气前神经元的经验，由于过度兴奋在外周化学反射通道表达的可塑性。模拟还表明，由于前Bötzinger复合体中的吸气前神经元与后斜方核中的呼气神经元之间的正相互作用，前者的兴奋性增加可能导致CIH暴露后发现的正常CO2水平下的主动呼气模式的出现。我们的结论是，神经元类型特异性神经可塑性的前Bötzinger复杂的外周化学感受器激活缺氧诱导的重复发作可能有助于交感神经过度活跃和高血压的发展。
The respiratory central pattern generator must respond to chemosensory cues to maintain oxygen (O2) and carbon dioxide (CO2) homeostasis in the blood and tissues. To do this, sensorial cells located in the periphery and central nervous system monitor the arterial partial pressure of O2 and CO2 and initiate respiratory and autonomic reflex adjustments in conditions of hypoxia and hypercapnia. In conditions of chronic intermittent hypoxia (CIH), repeated peripheral chemoreceptor input mediated by the nucleus of the solitary tract induces plastic changes in respiratory circuits that alter baseline respiratory and sympathetic motor outputs and result in chemoreflex sensitization, active expiration, and arterial hypertension. Herein, we explored the possibility that the CIH-induced neuroplasticity primarily consists of increased excitability of pre-inspiratory/inspiratory neurons in the pre-Bötzinger complex. To evaluate this hypothesis and elucidate neural mechanisms for the emergence of active expiration and sympathetic overactivity in CIH-treated animals, we extended a previously developed computational model of the brainstem respiratory-sympathetic network to reproduce experimental data on peripheral and central chemoreflexes post-CIH. The model incorporated neuronal connections between the 2nd-order NTS neurons and peripheral chemoreceptors afferents, the respiratory pattern generator, and sympathetic neurons in the rostral ventrolateral medulla in order to capture key features of sympathetic and respiratory responses to peripheral chemoreflex stimulation. Our model identifies the potential neuronal groups recruited during peripheral chemoreflex stimulation that may be required for the development of inspiratory, expiratory and sympathetic reflex responses. Moreover, our model predicts that pre-inspiratory neurons in the pre-Bötzinger complex experience plasticity of channel expression due to excessive excitation during peripheral chemoreflex. Simulations also show that, due to positive interactions between pre-inspiratory neurons in the pre-Bötzinger complex and expiratory neurons in the retrotrapezoid nucleus, increased excitability of the former may lead to the emergence of the active expiratory pattern at normal CO2 levels found after CIH exposure. We conclude that neuronal type specific neuroplasticity in the pre-Bötzinger complex induced by repetitive episodes of peripheral chemoreceptor activation by hypoxia may contribute to the development of sympathetic over-activity and hypertension.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
2.7
作者：
Braga, Valdir A.;Soriano, Renato N.;Machado, Benedito H.
通讯作者：
Machado, Benedito H.
影响因子：
5.5
作者：
Abdala, A. P. L.;Rybak, I. A.;Paton, J. F. R.
通讯作者：
Paton, J. F. R.
影响因子：
2.5
作者：
Costa-Silva, Joao H.;Zoccal, Daniel B.;Machado, Benedito H.
通讯作者：
Machado, Benedito H.
影响因子：
5.5
作者：
Koshiya, N;Guyenet, PG
通讯作者：
Guyenet, PG