Mechanisms Underlying Seasonal Adaptation of Daily Behaviors

每天的清醒-睡眠周期是动物生活的普遍特征，睡眠的中断与 人类的许多健康相关疾病。昼夜节律计时系统通常调节昼夜节律的时间。 根据动物是白天活动还是夜间活动，在一天中的特定时间醒来和睡觉。此外 昼夜节律的调节，每天的清醒-睡眠模式是由一个复杂的平衡之间的稳态 睡眠促进途径、唤醒回路、环境信号（例如，光和温度）和内部状态， 例如营养状况。在这个建议中，我们将使用果蝇作为模型系统，以了解如何每天 觉醒-睡眠周期适应环境条件的季节性变化，重点是相对 温度的不确定作用。温度对睡眠有广泛的影响， 果蝇和人类例如，许多白天活动的动物对温暖的温度的反应是增加 白天睡觉或“午睡”，几乎可以肯定是一种适应性反应，以尽量减少暴露在热。一个主要 我们的建议的基础是基于我们长期的工作表明，在D。melanogaster的温度- 3 '-末端内含子（称为dmpi 8）从称为周期的关键生物钟组分的依赖性剪接 (per)是一个突出的“温度传感器”，它可以调整每天的唤醒-睡眠周期的分布， 适当的回应。例如，在温暖的日子里，dmpi 8内含子的剪接在某种程度上是低效的， 更长的午休时间在最近的研究中，我们发现dmpi 8的热敏剪接 通过非昼夜节律机制调节日常活动的分布，该机制涉及感觉的变化， 介导的唤醒我们将采取多方面的实验策略，包括生物化学，分子， 细胞培养和整个动物的方法来表征这种新的觉醒/睡眠回路。

Daily wake-sleep cycles are a pervasive feature of animal life, and disruptions in sleep are associated with numerous health related disorders in humans. The circadian timing system generally regulates the timing of wake and sleep to specific times in the day depending on whether an animal is diurnal or nocturnal. In addition to circadian regulation, daily wake-sleep patterns are governed by a complex balance between homeostatic sleep promoting pathways, arousal circuits, environmental signals (e.g., light and temperature) and internal state, such as nutritional status. In this proposal we will use Drosophila as a model system to understand how daily wake-sleep cycles adapt to seasonal changes in environmental conditions, with an emphasis on the relatively uncharacterized role of temperature. Temperature has been shown to have widespread effects on sleep in both Drosophila and humans. For example, many diurnal animals respond to warm temperatures by increasing daytime sleep or ‘siesta’, almost certainly an adaptive response to minimize exposure to heat. A major foundation for our proposal is based on our long-standing work showing that in D. melanogaster the temperature- dependent splicing of the 3'-terminal intron (called dmpi8) from the key circadian clock component termed period (per) is a prominent ‘thermosensor’ that adjusts the distribution of daily wake-sleep cycles, eliciting seasonably appropriate responses. For example, on warm days splicing of the dmpi8 intron is inefficient somehow leading to a longer midday siesta. In more recent findings we showed that the thermosensitive splicing of dmpi8 modulates the distribution of daily activity via a non-circadian mechanism that involves changes in sensory- mediated arousal. We will undertake a multi-faceted experimental strategy that includes biochemical, molecular, cell-culture and whole animal approaches to characterize this novel arousal/sleep circuit.