丘脑底核旁核调控睡眠-觉醒的作用及机制

睡眠障碍已成为严重的社会和医学问题，失眠和焦虑互为因果，相互加重，但其机制不明。因此，阐明焦虑性失眠的机制是重要的科学问题。丘脑底核旁核位于外侧下丘脑的尾端、丘脑底核的旁边，主要由谷氨酸能神经元组成。丘脑底核旁核与调控焦虑的杏仁核交互投射，下游是臂旁核等。我们预实验发现特异性激活丘脑底核旁核的神经元，能诱导动物觉醒，作用持续4小时。因此，我们提出假说：丘脑底核旁核可能通过杏仁核和臂旁核等调控睡眠觉醒。本课题将采用化学遗传学、光遗传学、特异性神经元顺行和逆行示踪、电生理和免疫组化等方法，结合焦虑动物模型、睡眠脑电记录及焦虑行为分析平台，探索丘脑底核旁核在睡眠觉醒中的作用和对焦虑行为的影响。预期结果将揭示丘脑底核旁核调控焦虑性失眠的机制，对开发新的治疗策略提供理论依据。

Sleep disorders have become a serious social and medical problem. Insomnia and anxiety disorders interact each other, and intensify the symptoms of both. However, the mechanisms are unclear. Therefore, it is an important scientific question to elucidate the mechanism of insomnia with anxiety. The parasubthalamic nucleus (PSTN) is located at the end of the lateral hypothalamus, next to the subthalamic nucleus, and is mainly composed of glutamatergic neurons. PSTN has interactive projection with the amygdala, which modulating anxiety, and projects to the parabrachial nuclei. Our preliminary data showed that the specific activation of PSTN increased wakefulness lasting for 4 h. Therefore, we hypothesize that PSTN is a key brain region in sleep-wake regulation and anxiety through the parabrachial nuclei and amygdala. In these studies, we are going to determine the roles and mechanisms of PSTN in sleep-wake regulation using optogenetics and chemogenetics, special anterograde and retrograde tracers, electrophysiological, immunohistochemistry techniques, anxious animal model, sleep and anxiety bioassay systems. The expected results will reveal the mechanism of PSTN in regulating insomnia with anxiety, which may facilitate the development of novel treatments for comorbid sleep disturbance and anxiety.