Rest in Drosophila Is a Sleep-like State

Abstract

To facilitate the genetic study of sleep, we documented that rest behavior in Drosophila melanogaster is a sleep-like state. The animals choose a preferred location, become immobile for periods of up to 157 min at a particular time in the circadian day, and are relatively unresponsive to sensory stimuli. Rest is affected by both homeostatic and circadian influences: when rest is prevented, the flies increasingly tend to rest despite stimulation and then exhibit a rest rebound. Drugs acting on a mammalian adenosine receptor alter rest as they do sleep, suggesting conserved neural mechanisms. Finally, normal homeostatic regulation depends on the timeless but not the period central clock gene. Understanding the molecular features of Drosophila rest should shed new light on the mechanisms and function of sleep.

Video tracking and analysis of sleep in Drosophila melanogaster

“…This so-called crepuscular pattern of activity has been known since the early days -the very name Drosophila is Greek for "lover of the dew" -and the first systemic reports about the alternation of periods of activity and quiescence in adult Drosophila date back to 1956 1 . However, despite a long standing interest in the circadian regulation of Drosophila 50 activity, little was known about the biological characteristics of the mainly nocturnal resting state until the year 2000, when two independent laboratories demonstrated that the prolonged inactivity observed in Drosophila fully satisfies the five behavioural characteristics that define a sleep-like status 2 : (i) consolidated circadian periods of immobility, (ii) a species-specific posture and/or resting place, (iii) an increased arousal threshold, (iv) reversibility to wakefulness and (v) a 55 homeostatic regulatory mechanism 3,4 . We now know that sleep loss has similar detrimental effects on flies as it has on mammals 5,6 and that social experience modulates sleep need in Drosophila, as it does in vertebrates 7,8 .…”

“…Conservation of sleep from humans to flies extends beyond behaviour to pharmacology (e.g. : caffeine and amphetamines promote wakefulness 3,4 , whereas sedatives like hydroxyzine promote sleep 4 ) and flies, like vertebrates, show distinct electrophysiological correlates 60 of wakefulness and sleep in the brain neuronal activity 9 . Together, these findings demonstrate an evolutionary conservation between Drosophila and human sleep at the behavioural and molecular levels, making flies an ideal system to study the mysterious functions of sleep and all its connections to pathological conditions in humans.…”

“…The best way to distinguish locomotor rest from sleep is to measure arousal threshold. When flies are asleep, their arousal threshold increases and it is therefore possible to reliably infer if an animal is asleep by actively challenging it with a sensory stimulus, such as 145 tapping 3,16 or vibrating 4 the vial. The likelihood that a fly will respond to a complex stimulus levels off after five minutes of immobility 16 and for this reason sleep in flies is commonly defined as "a period of inactivity lasting at least five consecutive minutes".…”

“…It is possible to obtain robust sleep deprivation through 220 mechanical stimulation of flies: for instance, tapping the vials where the flies are housed whenever they stop moving 3 , spinning the flies upside down to interfere with their geotactic instincts 6,18 , or placing flies on a laboratory orbital rotator 19 . Manual sleep deprivation is efficient but incompatible with high throughput experimental conditions; automatic sleep deprivation provides a good compromise and can be achieved by placing the monitor in a 225 rotating device, which is relatively easy to build 18 , or on a common laboratory orbital shaker 19 • Socially-induced suppression of sleep.…”

Even a stopped clock tells the right time twice a day: circadian timekeeping in Drosophila

“…(2) The first four clock genes identified are non-essential genes with few roles outside the clock. Indeed, they seem dedicated to rhythmic processes, as their other reported effects include altered courtship song rhythms and recovery from sleep deprivation [20,21]. This can be contrasted with the first two learning and memory genes identified in Drosophila, dunce and rutabaga, which are essential genes with general roles in cyclic AMP signal transduction [reviewed in 22].…”