We have identified a group of ~20 neurons that can be activated on-demand using Drosophila genetics. The sleep observed during activation of these neurons meets the historical definition for identifying sleep. Our data highlight the importance of these neurons for regulating sleep. In this proposal we will use live-cell imaging and in vivo electrophysiological recording from Drosophila brains to define the properties of these neurons in the intact brain. The ability to use Drosophila genetics to induce sleep provides a unique opportunity to examine whether sleep can be used as a therapeutic for slowing or attenuating cognitive impairments associated with degenerative diseases. Thus, we will determine whether inducing sleep in Drosophila models of Parkinson's and Alzheimer's disease can offset deficits in cognitive behavior.

Public Health Relevance

Insufficient sleep and sleep disruption result in increased morbidity, mortality and may accelerate cognitive impairments during neurodegenerative disease. We propose to use genetics to functionally evaluate sleep promoting neurons during health and disease. We will determine whether sleep can mitigate or attenuate pathology in animal models of Alzheimer's and Parkinson's disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Molecular Neurogenetics Study Section (MNG)
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Gnadt, James W
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Washington University
Schools of Medicine
Saint Louis
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Ferguson, Lachlan; Petty, Alice; Rohrscheib, Chelsie et al. (2017) Transient Dysregulation of Dopamine Signaling in a Developing Drosophila Arousal Circuit Permanently Impairs Behavioral Responsiveness in Adults. Front Psychiatry 8:22
Sitaraman, Divya; Kramer, Elizabeth F; Kahsai, Lily et al. (2017) Discrete Serotonin Systems Mediate Memory Enhancement and Escape Latencies after Unpredicted Aversive Experience in Drosophila Place Memory. Front Syst Neurosci 11:92
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
LaFerriere, Holly; Zars, Troy (2017) The Drosophila melanogaster tribbles pseudokinase is necessary for proper memory formation. Neurobiol Learn Mem 144:68-76
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; 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
Dissel, Stephane; Melnattur, Krishna; Shaw, Paul J (2015) Sleep, Performance, and Memory in Flies. Curr Sleep Med Rep 1:47-54
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
Dissel, Stephane; Angadi, Veena; Kirszenblat, Leonie et al. (2015) Sleep restores behavioral plasticity to Drosophila mutants. Curr Biol 25:1270-81
Vanderheyden, William M; Gerstner, Jason R; Tanenhaus, Anne et al. (2013) ERK phosphorylation regulates sleep and plasticity in Drosophila. PLoS One 8:e81554

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