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，调节睡眠的遗传和神经机制仍然知之甚少。大多数睡眠研究都使用了夜间活动的哺乳动物，如小鼠和大鼠，但尚不清楚昼夜节律方面的睡眠调节是否与白天活动的哺乳动物（如人类）保持一致。我将利用相对简单但保守的神经回路和光学透明度的斑马鱼，一种昼夜脊椎动物，测试几个假设的作用，Prokineticin 2在调节睡眠和昼夜行为。首先，我将测试的假设，Prokineticin 2作为一个昼夜信号，以抑制运动活动，通过使用高通量运动活动和唤醒阈值测定进行增益和功能基因实验的损失。第二，我将测试的假设，Prokineticin 2神经元是活跃在晚上在斑马鱼幼虫使用生物发光报告，监测活动的遗传指定的神经元在自由行为的斑马鱼幼虫。第三，我将测试的假设，Prokinectin 2抑制唤醒促进神经元和激活促进睡眠的神经元，通过监测这些神经群体的活动，以响应Prokineticin 2过表达。这些实验有可能阐明介导昼夜节律输出和调节睡眠的神经机制，这可能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.