Thesis, COLLÉGIALITÉ

Abstract

Sleep is highly conserved across species and lack of it, as well as excess, can lead to multiple symptoms and diseases. Although it is essential to our survival, little is known about its mechanisms of regulation. In 2013, a genome-wide association study conducted by Allebrandt et al. showed a significant correlation between SUR2 polymorphism and sleep duration in humans. SUR2 is a regulatory subunit to an ATP-sensitive potassium channel and acts as a sensor of cellular energy metabolism. Pan-neuronal knock-down of its Drosophila homolog, dSUR, shows a significant sleep decrease. Our goal is to decipher dSUR-mediated sleep regulation by investigating the neuronal populations through which it acts and exploring its effect on sleep in Drosophila melanogaster. To this aim, we performed dSUR silencing using dSUR RNAi in different neuronal populations. We identified dopaminergic inputs to the mushroom body, the PAM neurons, to be the principal actors in dSUR-mediated sleep regulation. The mushroom body is a neuropil shown to play a role in associative learning and sleep. We performed a wide screening of the PAM neurons and identified subsets of them being wake-promoting and others being sleep-promoting. Moreover, we used MiMIC lines to localize dSUR expression in the Drosophila brain and found dSUR-positive neurons close to the mushroom body. Together, these results shed light on a potentially crucial actor in sleep regulation, SUR2, and its role in sleep homeostasis through dopaminergic circuitry. Further investigations will be needed to better understand its mechanisms of action and its eventual role as a linker between sleep and metabolism.