State-dependent control of breathing by the retrotrapezoid nucleus
State-dependent control of breathing by the retrotrapezoid nucleus
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DOI：
10.1113/jp270053
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发表时间：
2015-07-01
影响因子：
5.5
通讯作者：
Guyenet, Patrice G.
中科院分区：
文献类型：
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作者：
Burke, Peter G. R.;Kanbar, Roy;Guyenet, Patrice G.
在安静清醒、非快速眼动睡眠或快速眼动睡眠中，呼吸有不同的特征，包括对二氧化碳的不同依赖。我们调查了后梯形核(RTN)，一种质子敏感的结构，介导了高碳酸血症呼吸反射的很大一部分，是否在睡眠和清醒时调节呼吸的方式不同。记录28只清醒成年雄性SD大鼠的脑电、颈部肌电、血压、呼吸频率(f(R))和潮气量(V-T)。用通道视紫红质-2刺激RTN，或用古紫质抑制RTN，模拟中枢化学感受器活性的瞬时增加或减少。用含PRSX8启动子的慢病毒载体递送两种opsins。转导RTN和儿茶酚胺能神经元。在安静清醒或非REM睡眠中，高碳酸血症(3%或6%FI，CO2)可同时增加f(R)和V-T，而在REM睡眠中，高碳酸血症仅增加V-T。抑制RTN总是降低V-T，但仅在安静清醒和非REM睡眠时降低f(R)。刺激RTN总是增加V-T，但仅在安静清醒和非快速眼动睡眠时提高f(R)。血压不受刺激或抑制的影响。除快速眼动睡眠外，阶段性RTN刺激通过选择性地缩短吸气后相来吸引和缩短呼吸周期。时相刺激也会产生活跃的呼气，并减少早期呼气气流，但仅限于清醒时。当脑干模式发生器处于自动节律模式(麻醉、非快速眼动睡眠、安静清醒)时，V-T始终受RTN和CO2的调节，而f(R)仅受CO2和RTN的调节。REM睡眠期间RTN对呼吸的贡献减少，这可以解释为什么某些中枢性呼吸暂停在这个睡眠阶段较少发生。
Breathing has different characteristics during quiet wake, non-REM or REM sleep, including variable dependence on PCO2. We investigated whether the retrotrapezoid nucleus (RTN), a proton-sensitive structure that mediates a large portion of the hypercapnic ventilatory reflex, regulates breathing differently during sleep vs. wake. Electroencephalogram, neck electromyogram, blood pressure, respiratory frequency (f(R)) and tidal volume (V-T) were recorded in 28 conscious adult male Sprague-Dawley rats. Optogenetic stimulation of RTN with channelrhodopsin-2, or inhibition with archaerhodopsin, simulated an instantaneous increase or decrease of central chemoreceptor activity. Both opsins were delivered with PRSX8-promoter-containing lentiviral vectors. RTN and catecholaminergic neurons were transduced. During quiet wake or non-REM sleep, hypercapnia (3 or 6% FI,CO2 ) increased both f(R) and V-T whereas, in REM sleep, hypercapnia increased V-T exclusively. RTN inhibition always reduced V-T but reduced f(R) only during quiet wake and non-REM sleep. RTN stimulation always increased V-T but raised f(R) only in quiet wake and non-REM sleep. Blood pressure was unaffected by either stimulation or inhibition. Except in REM sleep, phasic RTN stimulation entrained and shortened the breathing cycle by selectively shortening the post-inspiratory phase. Phasic stimulation also produced active expiration and reduced early expiratory airflow but only during wake. V-T is always regulated by RTN and CO2 but f(R) is regulated by CO2 and RTN only when the brainstem pattern generator is in autorhythmic mode (anaesthesia, non-REM sleep, quiet wake). The reduced contribution of RTN to breathing during REM sleep could explain why certain central apnoeas are less frequent during this sleep stage.