Recent studies have identified the Drosophila brain circuits involved in the sleep/wake switch and have pointed to the modulation of neuronal excitability as one of the underlying mechanisms triggering sleep need. In this study we aimed to explore the link between the homeostatic regulation of neuronal excitability and sleep behavior in the circadian circuit. For this purpose, we selected the neuronal homeostasis protein Pumilio (Pum), whose main function is to repress protein translation and

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... s been linked to modulation of neuronal excitability during chronic patterns of altered neuronal activity. Here we explore the effects of Pum on sleep homeostasis in Drosophila melanogaster, which shares most of the major features of mammalian sleep homeostasis. Our evidence indicates that Pum is necessary for sleep rebound and that its effect is more pronounced during chronic sleep deprivation (84 hours) than acute deprivation (12 hours). Knockdown of pum, results in a reduction of sleep rebound during acute sleep deprivation and the complete abolishment of sleep rebound during chronic sleep deprivation. These behavioral changes were associated with accompanying changes in the expression of genes involved in the regulation of neuronal excitability. Interestingly, pum knockdown also increased baseline daytime sleep, suggesting that Pum differentially regulates rebound and normal sleep. Based on these findings, we propose that Pum is a critical regulator of sleep homeostasis through neural adaptations triggered during sleep deprivation and induces rebound sleep by altering neuronal excitability.