Regulation of Sleep and Circadian Behaviors by Prokineticin 2

类睡眠状态在整个进化过程中是保守的，慢性睡眠障碍影响了超过10%的人类。然而，调控睡眠的遗传和神经机制仍然知之甚少。大多数睡眠研究使用的是夜行性哺乳动物，如小鼠和大鼠，但目前尚不清楚睡眠调节的昼夜节律方面是否与人类等昼行性哺乳动物一致。我将利用斑马鱼（一种昼行性脊椎动物）相对简单但保守的神经回路和光学透明性，来测试关于Prokineticin 2在调节睡眠和昼夜节律行为中的作用的几个假设。首先，我将测试Prokineticin 2作为一个昼夜节律信号来抑制运动活动的假设，通过使用高通量运动活动和唤醒阈值分析进行功能的获得和丧失基因实验。其次，我将测试Prokineticin 2神经元在夜间在斑马鱼幼虫中活跃的假设，使用生物发光报告器来监测自由行为的斑马鱼幼虫中遗传指定神经元的活动。第三，我将通过监测Prokineticin 2过度表达时这些神经群的活动来测试Prokinectin 2抑制促进觉醒神经元并激活促进睡眠神经元的假设。这些实验有可能阐明调节昼夜节律输出和调节睡眠的神经机制，这可能会导致睡眠和昼夜节律相关疾病的新疗法。

Sleep-like states are conserved throughout evolution, and chronic sleep disorders affect over 10% of humans. However, the genetic and neural mechanisms that regulate sleep remain poorly understood. Most sleep studies have used nocturnal mammals such as mice and rats, but it is unclear whether circadian aspects of sleep regulation are conserved with diurnal mammals such as humans. I will exploit the relatively simple yet conserved neural circuits and optical transparency of the zebrafish, a diurnal vertebrate, to test several hypotheses regarding the role of Prokineticin 2 in regulating sleep and circadian behaviors. First, I will test the hypothesis that Prokineticin 2 acts as a circadian signal to inhibit locomotor activity by performing gain and loss of function genetic experiments using high throughput locomotor activity and arousal threshold assays. Second, I will test the hypothesis that Prokineticin 2 neurons are active at night in zebrafish larvae using a bioluminescence reporter that monitors the activities of genetically specified neurons in freely behaving zebrafish larvae. Third, I will test the hypothesis that Prokinectin 2 inhibits wake-promoting neurons and activates sleep-promoting neurons by monitoring the activities of these neural populations in response to Prokineticin 2 overexpression. These experiments have the potential to clarify the neural mechanisms that mediate circadian output and regulate sleep, which may lead to new therapies for sleep and circadian related disorders.