While the function of sleep remains a mystery, many of the most successful theories on sleep function, including synaptic downscaling, memory consolidation, developmental maturation, and even many theories on sleep restoration require that sleep must substantially influence aspects of brain plasticity. We demonstrate that increasing sleep restores brain functions supporting short-term memory in each of 12 classic memory mutants without specifically rescuing the causal molecular lesion or structural defect. We also demonstrate that sleep can rescue brain functions supporting long-term memory as assessed by courtship conditioning. Elucidating the underlying molecular mechanisms may shed new light on processes related to sleep function and may ultimately provide a roadmap for using sleep as a therapeutic to slow or reverse cognitive decline associated with degenerative disease and perhaps developmental disorders. Thus, in this proposal we will: 1) identify the circuits that are required to support sleep-dependent changes in adaptive behavior, 2) manipulate specific genes to determine if they are required for sleep induced restoration of memory, and 3) Determine whether the therapeutic role of sleep extends to disorders in which species of toxic proteins can actively impair neuronal functions and/or kill neurons.

Public Health Relevance

We have shown that sleep can restore plasticity to a large collection of well characterized mutants including in a Drosophila model of Alzheimer's disease. We propose to determine how sleep can benefit the brain so as to provide insights into how sleep might be used to slow or reverse cognitive decline associated with degenerative disease, psychiatric disorders.

National Institute of Health (NIH)
Research Project (R01)
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Molecular Neurogenetics Study Section (MNG)
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He, Janet
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Washington University
Schools of Medicine
Saint Louis
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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
Donlea, Jeffrey M; Ramanan, Narendrakumar; Silverman, Neal et al. (2014) Genetic rescue of functional senescence in synaptic and behavioral plasticity. Sleep 37:1427-37
Thimgan, Matthew S; Gottschalk, Laura; Toedebusch, Cristina et al. (2013) Cross-translational studies in human and Drosophila identify markers of sleep loss. PLoS One 8:e61016
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Donlea, Jeffrey; Leahy, Averi; Thimgan, Matthew S et al. (2012) Foraging alters resilience/vulnerability to sleep disruption and starvation in Drosophila. Proc Natl Acad Sci U S A 109:2613-8
Seugnet, Laurent; Suzuki, Yasuko; Donlea, Jeff M et al. (2011) Sleep deprivation during early-adult development results in long-lasting learning deficits in adult Drosophila. Sleep 34:137-46
Donlea, Jeffrey M; Thimgan, Matthew S; Suzuki, Yasuko et al. (2011) Inducing sleep by remote control facilitates memory consolidation in Drosophila. Science 332:1571-6
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Thimgan, Matthew S; Suzuki, Yasuko; Seugnet, Laurent et al. (2010) The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss. PLoS Biol 8:
Donlea, Jeffrey M; Ramanan, Narendrakumar; Shaw, Paul J (2009) Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Science 324:105-8

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