The Drosophila Circadian Clock Gates Sleep through Time-of-Day Dependent Modulation of Sleep-Promoting Neurons.
OBJECTIVE
Sleep is under the control of homeostatic and circadian processes, which interact to determine sleep timing and duration, but the mechanisms through which the circadian system modulates sleep are largely unknown. We therefore used adult-specific, temporally controlled neuronal activation and inhibition to identify an interaction between the circadian clock and a novel population of sleep-promoting neurons in Drosophila.


METHODS
Transgenic flies expressed either dTRPA1, a neuronal activator, or Shibire(ts1), an inhibitor of synaptic release, in small subsets of neurons. Sleep, as determined by activity monitoring and video tracking, was assessed before and after temperature-induced activation or inhibition using these effector molecules. We compared the effect of these manipulations in control flies and in mutant flies that lacked components of the molecular circadian clock.


RESULTS
Adult-specific activation or inhibition of a population of neurons that projects to the sleep-promoting dorsal Fan-Shaped Body resulted in bidirectional control over sleep. Interestingly, the magnitude of the sleep changes were time-of-day dependent. Activation of sleep-promoting neurons was maximally effective during the middle of the day and night, and was relatively ineffective during the day-to-night and night-to-day transitions. These time-ofday specific effects were absent in flies that lacked functional circadian clocks.


CONCLUSIONS
We conclude that the circadian system functions to gate sleep through active inhibition at specific times of day. These data identify a mechanism through which the circadian system prevents premature sleep onset in the late evening, when homeostatic sleep drive is high.
Penn Chronobiology Program, Philadelphia PA.|Current Address: Department of Biology, Loyola University Chicago, Chicago IL.
Daniel J
DJ
Cavanaugh
Penn Chronobiology Program, Philadelphia PA.
Abigail S
AS
Vigderman
Penn Chronobiology Program, Philadelphia PA.
Terry
T
Dean
Penn Chronobiology Program, Philadelphia PA.
David S
DS
Garbe
Penn Chronobiology Program, Philadelphia PA.|Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia PA.
Amita
A
Sehgal
D000818:Animals; D030801:Animals, Genetically Modified; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D034281:Dynamins / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D007473:Ion Channels; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D029721:Drosophila Proteins; D007473:Ion Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; D034281:Dynamins; C439628:shi protein, Drosophila
Drosophila; circadian clock; sleep