Mechanisms Underlying Seasonal Adaptation of Daily Behaviors

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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.