Neural circuitry of stress-induced insomnia in rats.
Neural circuitry of stress-induced insomnia in rats.
复制标题
DOI：
10.1523/jneurosci.1809-08.2008
复制
发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Saper CB
中科院分区：
文献类型：
--
作者：
Cano G;Mochizuki T;Saper CB
在发生压力事件之后，睡眠建筑通常会受到干扰。然而，对于负责由压力引起的睡眠扰动的脑电路知之甚少。我们将大鼠暴露于最初引起急性应激反应的心理压力源（笼子交换），但几个小时后产生与人类压力引起的失眠相似的睡眠障碍模式：增加了睡眠潜伏期，NREM降低和REM睡眠，在NREM睡眠期间增加碎片化和高频脑电图活性。我们检查了FOS表达的模式，以识别激活的大脑电路，并发现在大脑皮层，边缘系统以及唤醒和自主系统的一部分中增加了FOS。令人惊讶的是，促进睡眠的地区同时激活了昼夜节压力和稳态压力的驱动。在NREM睡眠期间，脑皮质和唤醒系统的活性在睡眠时产生了一种新型的中间状态，其特征是脑电图高频活性（与醒来的特征）。离散边缘和唤醒区域的失活允许恢复特定的睡眠组件并改变了FOS模式，这表明边缘区域的分层组织又激活了唤醒系统，然后激活了大脑皮层，从而产生了高频活性。在唤醒系统的部分失活后，在压力大鼠中消除了NREM期间的这种高频活性。这些结果表明，关闭边缘隔离系统的残留活性可能是治疗压力引起的失眠而不是增强睡眠系统的更好方法，而睡眠系统仍然充分活跃。
Sleep architecture is often disturbed following a stressful event; nevertheless, little is known about the brain circuitry responsible for the sleep perturbations induced by stress. We exposed rats to a psychological stressor (cage exchange) that initially causes an acute stress response, but several hours later generates a pattern of sleep disturbances similar to that observed in stress-induced insomnia in humans: increased sleep latency, decreased nREM and REM sleep, increased fragmentation, and high frequency EEG activity during nREM sleep. We examined the pattern of Fos expression to identify the brain circuitry activated, and found increased Fos in the cerebral cortex, limbic system, and parts of the arousal and autonomic systems. Surprisingly, there was simultaneous activation of the sleep-promoting areas, most likely driven by ongoing circadian and homeostatic pressure. The activity in the cerebral cortex and arousal system while sleeping generates a novel intermediate state characterized by EEG high frequency activity, distinctive of waking, during nREM sleep. Inactivation of discrete limbic and arousal regions allowed the recovery of specific sleep components and altered the Fos pattern, suggesting a hierarchical organization of limbic areas that in turn activate the arousal system and subsequently the cerebral cortex, generating the high frequency activity. This high frequency activity during nREM was eliminated in the stressed rats after inactivating parts of the arousal system. These results suggest that shutting down the residual activity of the limbic-arousal system might be a better approach to treat stress-induced insomnia rather than potentiation of the sleep system, which remains fully active.