Although the precise function of sleep remains unknown, there is little question that sleep is required for maintaining optimal performance in a large and diverse number of biological systems. Indeed, cognitive impairments associated with aging and neurodegenerative disorders are frequently accompanied by deficits in sleep physiology and architecture. We have previously shown that enhanced sleep can reverse memory deficits even in flies with catastrophic lesions to their primary memory center. We have now mapped a minimal circuitry required by this memory assay. Using genomics and behavioral genetics we have identified genes that can restore memory when they are modulated in a single circuit-component in a similar fashion as that produced by sleep. In this proposal we will determine the molecular pathways that regulate these genes. In addition, we will use calcium imaging to determine how restoring a single circuit component modulates the activity of other circuit components to restore memory during brain damage or the expression of Human Alzheimer's' related genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051305-16
Application #
9902560
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
He, Janet
Project Start
2005-04-01
Project End
2024-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
16
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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; 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
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

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