CONTEXT-DEPENDENT REGULATION OF SLEEP MEDIATED BY ENDOCRINE HORMONES AND RNA PROCESSING

Sleep is a natural state of rest that is prevalent among most animals and characterized by some common traits. It is primarily regulated by the circadian clock and by a homeostatic system that drives the need to sleep, and the traditional focus has been on neuronal roles of sleep in the brain. This thesis used a Drosophila model to dissect the mechanisms, central and peripheral, that modulate sleep under different conditions. In Chapter 1, we discuss recent research that glia, non-neuronal cells in the brain, and the periphery also play a role in sleep regulation. In particular, the endocrine system, which is a primary communication system between the brain and the periphery, may participate in sleep regulation. In Chapter 2, we conducted a screening of all endocrine nuclear hormone receptors (NHRs) in Drosophila and identified the peripheral derived steroid hormone ecdysone, with its receptor EcR, as important regulators of sleep. We found that ecdysone enhances sleep by mobilizing lipid droplets in a specific glial subtype, cortex glia. As ecdysone is responsive to environmental and metabolic factors, its regulation of sleep may provide a mechanism for adapting sleep to different contexts. In Chapter 3, we investigated the interplay between sleep and cognitive tasks, as sleep is known to promote higher-order cognitive processes, like learning and memory consolidation, and conversely learning can induce sleep need in some conditions. Using a transcriptomic study of a specific population of cells involved in olfactory memory consolidation and post-learning sleep, we identified two genes for ribosomal RNA synthesis and mRNA decay, respectively, as important regulators of sleep. In Chapter 4, we summarize our findings on these two different mechanisms of context-dependent sleep regulation and discuss the future directions and broader implications of our work.