Sleep is controlled by two processes: a homeostatic drive that increases during waking and dissipates during sleep and a circadian pacemaker that controls its timing. Although these two systems can operate independently recent studies suggest a more intimate relationship. Indeed, none has been as dramatic as that found for the canonical loss-of-function clock mutant cycle (cyc01). cyc01 mutants showed a disproportionately large sleep rebound and died following 10 hours of sleep deprivation, although they were more resistant than other clock mutants to various stressors. Our data indicate that the pathology is characterized by an acceleration of the detrimental effects of waking and furthermore, suggests that these processes subsequently increase the need for sleep (Shaw et al., 2002). Using genomic studies in these uniquely sensitive animals, we have begun to identify functional targets of sleep homeostasis and its molecular mechanisms. Thus we know of 100 genes that are modulated by prolonged wakefulness. In order to more fully understand the role these genes play, we will determine their temporal dynamics in response to increasing amounts of waking. Moreover, because we have developed independent genetic, pharmacological and behavioral assays that produce periods of waking that differentially activate homeostatic responses, we will determine the extent to which these genes are specifically associated with homeostasis. More importantly, we have acquired over 110 mutant lines representing approximately 60 of the 100 genetic loci of interest and have begun to evaluate their sleep parameters and responses to sleep deprivation. We propose to characterize select genes further by localizing mRNA and protein expression and to manipulate the activity of these genes and the cells that express them by creating a variety of useful transgenic lines using UAS, GAL4 and GAL80 vectors.
| Yap, Melvyn H W; Grabowska, Martyna J; Rohrscheib, Chelsie et al. (2017) Oscillatory brain activity in spontaneous and induced sleep stages in flies. Nat Commun 8:1815 |
| Dissel, Stephane; Klose, Markus; Donlea, Jeff et al. (2017) Enhanced sleep reverses memory deficits and underlying pathology in Drosophila models of Alzheimer's disease. Neurobiol Sleep Circadian Rhythms 2:15-26 |
| Seugnet, Laurent; Dissel, Stephane; Thimgan, Matthew et al. (2017) Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss. Front Neural Circuits 11:79 |
| Dissel, Stephane; Seugnet, Laurent; Thimgan, Matthew S et al. (2015) Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption. Brain Behav Immun 47:75-85 |
| Thimgan, Matthew S; Seugnet, Laurent; Turk, John et al. (2015) Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila. Sleep 38:801-14 |
| Dissel, Stephane; Melnattur, Krishna; Shaw, Paul J (2015) Sleep, Performance, and Memory in Flies. Curr Sleep Med Rep 1:47-54 |
| Dissel, Stephane; Angadi, Veena; Kirszenblat, Leonie et al. (2015) Sleep restores behavioral plasticity to Drosophila mutants. Curr Biol 25:1270-81 |
| Faville, R; Kottler, B; Goodhill, G J et al. (2015) How deeply does your mutant sleep? Probing arousal to better understand sleep defects in Drosophila. Sci Rep 5:8454 |
| Lucey, Brendan P; Leahy, Averi; Rosas, Regine et al. (2015) A new model to study sleep deprivation-induced seizure. Sleep 38:777-85 |
| Thimgan, Matthew S; Toedebusch, Cristina; McLeland, Jennifer et al. (2015) Excessive daytime sleepiness is associated with changes in salivary inflammatory genes transcripts. Mediators Inflamm 2015:539627 |
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