State-Dependent Modulation of Breathing in Urethane-Anesthetized Rats
State-Dependent Modulation of Breathing in Urethane-Anesthetized Rats
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DOI：
10.1523/jneurosci.0948-12.2012
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发表时间：
2012-08-15
影响因子：
5.3
通讯作者：
Dickson, Clayton T.
中科院分区：
文献类型：
--
作者：
Pagliardini, Silvia;Greer, John J.;Dickson, Clayton T.
呼吸活动在睡眠期间最脆弱，特别是在反常睡眠[或快速眼动(REM)]睡眠和睡眠状态转换期间。大鼠通常被用来研究呼吸神经调节，但啮齿动物的睡眠具有高度碎片化的睡眠模式，这使得研究不同的睡眠状态和其中潜在的药物操作非常具有挑战性。在乌拉坦麻醉下，大鼠会发生类似睡眠的脑状态变化，这可能是一种有效的睡眠模型。本研究评估了乌拉坦麻醉下呼吸和呼吸肌调节的状态依赖性变化，以确定它们与自然睡眠中发生的相似之处。用乌拉坦和呼吸气流麻醉大鼠，记录呼吸肌的肌电活动，结合大脑皮层和海马区的局部场电位，确定呼吸模式和肌肉活动是如何随脑状态而调节的。测量是在常氧、低氧和高碳酸血症条件下进行的。结果与老鼠在自然睡眠中的录音进行了比较。乌拉坦麻醉下的脑状态改变与呼吸频率和变异性的改变以及呼吸肌张力的调节密切相关。这些变化与在自然睡眠中观察到的变化非常相似。有趣的是，在快速眼动和类快速眼动状态下，颧舌肌活动受到强烈抑制，腹肌活动表现出强烈的呼气调节。我们证明，在乌拉坦麻醉的大鼠中，呼吸气流和肌肉活动与脑状态转换密切相关，并与自然睡眠中的变化相似，为系统研究与睡眠相关的呼吸控制变化提供了一个有用的模型。
Respiratory activity is most fragile during sleep, in particular during paradoxical [or rapid eye movement (REM)] sleep and sleep state transitions. Rats are commonly used to study respiratory neuromodulation, but rodent sleep is characterized by a highly fragmented sleep pattern, thus making it very challenging to examine different sleep states and potential pharmacological manipulations within them. Sleep-like brain-state alternations occur in rats under urethane anesthesia and may be an effective and efficient model for sleep itself. The present study assessed state-dependent changes in breathing and respiratory muscle modulation under urethane anesthesia to determine their similarity to those occurring during natural sleep. Rats were anesthetized with urethane and respiratory airflow, as well as electromyographic activity in respiratory muscles were recorded in combination with local field potentials in neocortex and hippocampus to determine how breathing pattern and muscle activity are modulated with brain state. Measurements were made in normoxic, hypoxic, and hypercapnic conditions. Results were compared with recordings made from rats during natural sleep. Brain-state alternations under urethane anesthesia were closely correlated with changes in breathing rate and variability and with modulation of respiratory muscle tone. These changes closely mimicked those observed in natural sleep. Of great interest was that, during both REM and REM-like states, genioglossus muscle activity was strongly depressed and abdominal muscle activity showed potent expiratory modulation. We demonstrate that, in urethane-anesthetized rats, respiratory airflow and muscle activity are closely correlated with brain-state transitions and parallel those shown in natural sleep, providing a useful model to systematically study sleep-related changes in respiratory control.