Essential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration.
Essential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration.
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DOI：
10.1523/jneurosci.3141-10.2010
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Gourine AV
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文献类型：
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作者：
Marina N;Abdala AP;Trapp S;Li A;Nattie EE;Hewinson J;Smith JC;Paton JF;Gourine AV
位于脑干腹外侧的后梯形核（RTN）表达phox2b的神经元对PCO2/pH的变化敏感，对中枢呼吸节律/模式产生兴奋性投射，其激活增强中枢呼吸驱动。利用体内（清醒和麻醉的大鼠）和原位（动脉灌注的大鼠脑干-脊髓制剂）模型，我们评估了这些神经元群在静息呼吸活动和二氧化碳引起的呼吸反应中的功能意义，在慢病毒构建体转导后，使用昆虫肽allatostatin表达g蛋白偶联果蝇allatostatin受体，从而可逆地抑制这些神经元。allatostatin选择性抑制包括RTN在内的腹外侧脑干phox2b表达神经元对清醒大鼠静息呼吸活动无影响，但降低了麻醉大鼠和原位大鼠制剂中膈神经放电幅度。吸气后的活动也在原位降低。在没有或存在外周化学受体输入的情况下，抑制高碳酸血症期间表达phox2b的神经元可消除麻醉大鼠和原位制剂中co2诱发的腹呼气活动。在颈动脉失神经的麻醉大鼠和外周化学感受器完好的清醒大鼠中，呼吸空气中二氧化碳水平升高所引起的吸入反应也分别减少了28%和60%。这些数据表明，中枢呼气驱动关键依赖于腹侧脑干中表达phox2b的神经元，并支持这些神经元在二氧化碳诱发的吸气活动增加中起重要作用的假设。
Phox2b-expressing neurons of the retrotrapezoid nucleus (RTN) located in the ventrolateral brainstem are sensitive to changes in PCO2/pH, have excitatory projections to the central respiratory rhythm/pattern generator and their activation enhances central respiratory drive. Using in vivo (conscious and anesthetized rats) and in situ (arterially-perfused rat brainstem-spinal cord preparations) models, we evaluated the functional significance of this neuronal population for both resting respiratory activity and the CO2-evoked respiratory responses by reversibly inhibiting these neurons using the insect peptide allatostatin following transduction with a lentiviral construct to express the G-protein-coupled Drosophila allatostatin receptor. Selective inhibition of the Phox2b-expressing neurons in the ventrolateral brainstem including the RTN using allatostatin was without effect on resting respiratory activity in conscious rats, but decreased the amplitude of the phrenic nerve discharge in anesthetized rats and the in situ rat preparations. Post-inspiratory activity was also reduced in situ. In the absence or presence of the peripheral chemoreceptor input, inhibiting the Phox2b-expressing neurons during hypercapnia abolished the CO2-evoked abdominal expiratory activity in anesthetized rats and in situ preparations. Inspiratory responses evoked by rising levels of CO2 in the breathing air were also reduced in anesthetized rats with denervated carotid bodies and conscious rats with peripheral chemoreceptors intact (by 28% and 60%, respectively). These data indicate a crucial dependence of central expiratory drive upon Phox2b-expressing neurons of the ventrolateral brainstem and support the hypothesis that these neurons contribute in a significant manner to CO2-evoked increases of inspiratory activity.