Exploiting the Power of Sleep to Rescue Long-Term Memory Defects in a Drosophila Memory Mutant
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Sleep is a behavior indispensable for life that is evolutionarily conserved throughout the animal kingdom, signifying its importance. Investigations into the function(s) of sleep reveal a vast array of processes influenced and bolstered by sleep, from the cellular level to whole-body functioning. Memory is another behavior indispensable for life that is also conserved throughout the animal kingdom. Short-term and long-term memory work collectively to generate associations that can inform future decision making and influence the survival of organisms. Sleep and memory have been shown to interact in a reciprocal relationship, either supportively or destructively, indicating that these behaviors are not mutually exclusive. Drosophila melanogaster has emerged as a powerful model organism to study sleep, memory, and their interaction. Sharing significant genetic homology in both physiological function and disease states, in addition to its formidable genetic toolbox, the fruit fly has provided ingresses into probing the nebulous realm of sleep- and memoryrelated processes. Previous studies have shown that pharmacological sleep induction with gaboxadol both prior to and following training can restore courtship long-term memory in the Drosophila memory mutant rutabaga. To identify the sleep-related center responsible for long-term memory restoration, we employed CsChrimson optogenetic activation using sleep-center specific Split-GAL4 lines to recapitulate memory restoration. All three sleep centers examined, the dorsal fan-shaped body, ventral nerve cord – sleep promoting, and ventral fan-shaped body, restored courtship long-term memory only when activated both prior to and following training. We found that pre-training activation restored the ability of memory mutants to form short-term memory in a sleep-independent manner, while posttraining activation restored consolidation into long-term memory in a sleep-dependent manner. We also found significant connectivity between these three sleep-related centers and the established courtship long-term memory circuit, and that the ventral fan-shaped body is indispensable for long-term memory restoration, regardless of sleep center activated. While attempting to extend this interaction into another memory paradigm, we identified several opportunities for optimization within an established appetitive visual memory assay. By addressing sexually dimorphic, color combination, and video-recording elements, we present an optimized, sex-specific paradigm that generates significant learning in fewer replications and numbers of flies.
Table of Contents
Sleep, memory, and their interaction -- Drosophila melanogaster as a model for sleep and memory investigations --Methods -- Restoration of courtship LTM using sleep derived from three distinct sleep-related centers -- Elucidating the circuitry by which sleep restores courtship LTM -- Optimization of an appetitive visual memory paradigm to study the interaction of sleep and memory -- Discussion
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Ph.D. (Doctor of Philosophy)