Genetic and Anatomical Regulation of Sleep in Drosophila: A Role for the Mushroom Bodies, Circadian Neurons, and the Gene, Clock, in Sleep PromotionPublic Deposited
After nearly 100 years of research, the function of sleep is unknown, prompting the desire to examine its regulation in a simpler model organism. In 2000, <em>Drosophila</em> was described as a novel model system to investigate sleep. These early studies defined features of normal sleep in <em>Drosophila</em>, and presented evidence that sleep was regulated genetically, since mutations in circadian genes affected the quantity and quality of fly sleep. However, it was unknown at the start of this thesis research whether sleep was a neuroanatomically regulated behavior, and actively promoted by the brain, as in mammals. To examine this possibility, we undertook an anatomical screen whereby various regions of the fly brain were examined for a sleep-regulatory function. The data presented here support a role for the <em>Drosophila</em> mushroom bodies (Chapter 2,3) and circadian circuitry (Chapter 3,4) as sleep regulatory regions important for sleep promotion, and a potential role for specific regions of the mushroom bodies and/or central complex in wake-promotion (Chapter 3). We also examined the role of the circadian gene <em>Clock</em> in sleep by assessing multiple mutant alleles, the contribution of genetic background to the phenotype, and the specificity of the <em>Clock</em> mutant sleep phenotype (Chapter 4). Importantly, we were able to rescue components of the <em>Clock</em> sleep phenotype by rescuing <em>Clock</em> function within mushroom body and circadian neurons (Chapter 4). These data provide the first evidence that sleep is neuroanatomically regulated in flies, as in mammals, and may be both actively promoted and inhibited. The data further suggest a genetic and anatomical link between circadian and sleep regulatory regions in the fly brain through <em>Clock</em>. Together, these data suggest that searching for genes expressed in the mushroom body, or <em>Clock</em> target genes might be a successful strategy to use in gene discovery, and to ultimately uncover the function of sleep.