任务状态下前额叶皮层控制觉醒的神经生物学机制

睡眠障碍问题日益严重。在休息期，机体进入睡眠，如有任务必须完成，仍能对抗睡眠，保持长时间清醒并处于工作状态。但是，任务状态下高级中枢控制觉醒行为的机制有待阐明。前额叶皮层（PFC）被认为是执行功能的中枢，在进行工作任务时皮层兴奋性增高。PFC向纹状体、下丘脑、丘脑等皮层下结构投射。我们前期发现，作为PFC最主要信息出口之一的纹状体在睡眠觉醒及目标导向型行为中发挥重要作用。因此提出假说：任务状态下，PFC-纹状体等皮层下结构的神经回路在大脑皮层控制觉醒过程中发挥关键作用。本研究将运用睡眠觉醒自动解析平台、光遗传和化学遗传法、四环素诱导调控表达系统、超微钙成像和电生理等技术，揭示任务状态下PFC控制觉醒的关键类型神经元，阐明PFC控制皮层下核团调控觉醒的神经环路和递质机制。预期结果将提出皮层自上而下调控觉醒新理论，为理解失眠发病机制、探索临床失眠治疗方案提供理论支撑及干预靶点。

Sleep disorders have become a serious social and medical problem. Generally, people sleep at night due to high sleep pressure. When there are ongoing assignment or task needing to be finished, the sleep could be counteracted and wake could be kept. However, the neural mechanisms underlying the brain controls wakefulness under task conditions remains to be clarified. The prefrontal cortex (PFC) is in charge of abstract thinking and thought analysis, and responsible for regulating behavior by its long-range connections with many subcortical structures, such as the striatum, the thalamus, and the hypothalamus. The neurons in the PFC mainly project to the striatum of the basal ganglia which has been demonstrated to play an important role in sleep-wake regulation and goal-directed behaviors. Therefore, we hypothesized that PFC-striatal pathway plays a crucial role in control of arousal and related behaviors for the task instance. Here we will apply the automatic sleep-wake analysis system, gene-manipulated mice, optogenetics and chemogenetics, tetracycline-controlled transcriptional system, miniature scope of calcium imaging in vivo, and electrophysiology to reveal the key neuronal types, neuron circuits, and neurotransmitters for the wakefulness controlled by the PFC under task conditions. The expected results will provide strong evidence to produce a novel theory for top-down control of wakefulness and be helpful in understanding insomnia pathogenesis.