Hyper-Activation of mPFC Underlies Specific Traumatic Stress-Induced Sleep-Wake EEG Disturbances
Hyper-Activation of mPFC Underlies Specific Traumatic Stress-Induced Sleep-Wake EEG Disturbances
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DOI：
10.3389/fnins.2020.00883
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发表时间：
2020-08-18
影响因子：
4.3
通讯作者：
Liu, Qinghua
中科院分区：
文献类型：
--
作者：
Lou, Tingting;Ma, Jing;Liu, Qinghua
睡眠障碍被认为是创伤后应激障碍（PTSD）的核心症状。然而，PTSD相关睡眠障碍的神经基础仍不清楚。建立特定脑区与创伤性应激诱导的睡眠异常之间的因果关系一直具有挑战性。在这里，我们发现，单次长时间应激（SPS）可以诱导急性变化的睡眠/觉醒时间以及短期和长期脑电图（EEG）的改变在同基因小鼠模型。此外，内侧前额叶皮质（mPFC）表现出持续高数量的c-fos表达神经元，其中超过95%是兴奋性神经元，在SPS期间和之后立即。在SPS过程中对mPFC边缘前区的化学发生抑制可以特异性地逆转SPS引起的非快速眼动睡眠（NREMS）δ功率（1-4 Hz EEG）的急性抑制以及大多数长期EEG异常。这些研究结果表明，mPFC神经元的过度激活和创伤性应激诱导的特定睡眠-觉醒EEG紊乱之间存在因果关系。
Sleep disturbances have been recognized as a core symptom of post-traumatic stress disorders (PTSD). However, the neural basis of PTSD-related sleep disturbances remains unclear. It has been challenging to establish the causality link between a specific brain region and traumatic stress-induced sleep abnormalities. Here, we found that single prolonged stress (SPS) could induce acute changes in sleep/wake duration as well as short- and long-term electroencephalogram (EEG) alterations in the isogenic mouse model. Moreover, the medial prefrontal cortex (mPFC) showed persistent high number of c-fos expressing neurons, of which more than 95% are excitatory neurons, during and immediately after SPS. Chemogenetic inhibition of the prelimbic region of mPFC during SPS could specifically reverse the SPS-induced acute suppression of delta power (1-4 Hz EEG) of non-rapid-eye-movement sleep (NREMS) as well as most of long-term EEG abnormalities. These findings suggest a causality link between hyper-activation of mPFC neurons and traumatic stress-induced specific sleep-wake EEG disturbances.