Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS076980-03
Application #
8517844
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
He, Janet
Project Start
2011-09-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$282,344
Indirect Cost
$58,009

  Institution

Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Baggett, Vincent; Mishra, Aditi; Kehrer, Abigail L et al. (2018) Place learning overrides innate behaviors inDrosophila. Learn Mem 25:122-128
Troup, Michael; Yap, Melvyn Hw; Rohrscheib, Chelsie et al. (2018) Acute control of the sleep switch in Drosophila reveals a role for gap junctions in regulating behavioral responsiveness. Elife 7:
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
Ferguson, Lachlan; Petty, Alice; Rohrscheib, Chelsie et al. (2017) Transient Dysregulation of Dopamine Signaling in a DevelopingDrosophilaArousal Circuit Permanently Impairs Behavioral Responsiveness in Adults. Front Psychiatry 8:22
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
LaFerriere, Holly; Zars, Troy (2017) The Drosophila melanogaster tribbles pseudokinase is necessary for proper memory formation. Neurobiol Learn Mem 144:68-76
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
Kirszenblat, Leonie; van Swinderen, Bruno (2015) The Yin and Yang of Sleep and Attention. Trends Neurosci 38:776-786
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

Showing the most recent 10 out of 16 publications