Department of Physiology, Centre for Neuroscience, and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
J Neurosci. 2012 Aug 15;32(33):11259-70. doi: 10.1523/JNEUROSCI.0948-12.2012.
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.
呼吸活动在睡眠期间最为脆弱，特别是在反常[或快速眼动（REM）]睡眠和睡眠状态转换期间。大鼠常用于研究呼吸神经调节，但啮齿动物的睡眠模式具有高度碎片化的特点，因此很难检查不同的睡眠状态及其潜在的药理学干预。在 Urethane 麻醉下，大鼠会出现类似睡眠的脑状态交替，这可能是睡眠本身的有效且高效模型。本研究评估了 Urethane 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期间发生的变化的相似性。用 Urethane 麻醉大鼠，同时记录呼吸气流以及呼吸肌的肌电图活动，并结合新皮层和海马中的局部场电位，以确定呼吸模式和肌肉活动如何随脑状态而调节。在正常氧、低氧和高碳酸血症条件下进行测量。结果与大鼠自然睡眠期间的记录进行了比较。Urethane 麻醉下的脑状态交替与呼吸频率和变异性的变化以及呼吸肌张力的调节密切相关。这些变化与自然睡眠中观察到的变化非常相似。非常有趣的是，在 REM 和 REM 样状态下，颏舌肌活动均被强烈抑制，而腹肌活动则表现出强烈的呼气调节。我们证明，在 Urethane 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，与自然睡眠中显示的状态相似，为系统研究与呼吸控制相关的睡眠变化提供了有用的模型。
