0232 Variation in Response to Sleep Deprivation in Drosophila Melanogaster

Abstract Introduction Sleep deprivation is known to negatively impact cognitive performance, metabolism, and immune responses, yet the genetic basis for variability in the response to sleep loss is not fully understood. Methods To address this gap in our knowledge, we assessed sleep behavior across more than 100 Drosophila melanogaster lines from the Drosophila Genetic Reference Panel 3 (DGRP3), with the goal of analyzing 252 distinct genotypes. We measured sleep and activity over two undisturbed days, followed by 12 hours of mechanical sleep deprivation. We then recorded recovery sleep over two subsequent days. We tested each genotype in three independent replicates, and used the Canton-S B strain as a control in every experiment. Results Our results confirm that the sleep deprivation protocol was effective, as all genotypes experienced sleep loss, and there was variation in the degree of sleep rebound observed the following day. Notably, only a small proportion (7%) of genotypes did not exhibit sleep rebound. Heritability estimates for total sleep over the five-day experimental period ranged from 0.39 to 0.50, indicating a considerable genetic component influencing sleep behavior. Both genotype and sex were found to be significant factors in shaping behavioral responses to sleep deprivation, supporting the prospect of mapping these traits genetically. Furthermore, incubator-specific effects were detected for the Canton-S B controls, highlighting the contribution of environmental factors to sleep variation. Conclusion In the future, we will utilize the genetic information available for the DGRP3 lines to conduct genome-wide association studies aimed at pinpointing genetic variants linked to resilience against sleep deprivation. We will perform subsequent functional studies to validate candidate genes. Taken together, this research will enhance our understanding of the genetic determinants that drive variability in sleep deprivation responses. Support (if any) This work was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute.