Effects of D-amino acids on sleep in Drosophila.

Sleep and metabolism are closely related and nutritional elements such as sugars and amino acids are known to regulate sleep differently. Here we comprehensively investigated the effects of D-amino acids fed in the diet on the sleep of Drosophila melanogaster. Among 19 amino acids examined, both D-serine (Ser) and D-glutamine (Gln) induced a significant increase in sleep amount and the effect of D-Ser was the largest at the same concentration of 1% of the food. The effects were proportional to its concentration and significant above 0.5% (about 50 mM). D-Ser is known to bind NR1 subunit of NMDA type glutamate receptor (NMDAR) and activate it. D-Ser did not increase the sleep of the NR1 hypomorphic mutant flies indicating its effects on sleep is mediated by NMDAR. In addition, hypomorphic mutants of D-amino acid oxidase (Daao1), which catabolizes D-amino acids and its disruption is known to increase D-Ser in the brain, showed increase in sleep. These results altogether suggested that D-Ser activated NMDAR in the brain thus increase sleep, and that D-Ser work physiologically to regulate sleep.

Protocerebral Bridge Neurons That Regulate Sleep in Drosophila melanogaster.

The central complex is one of the major brain regions that control sleep in Drosophila. However, the circuitry details of sleep regulation have not been elucidated yet. Here, we show a novel sleep-regulating neuronal circuit in the protocerebral bridge (PB) of the central complex. Activation of the PB interneurons labeled by the R59E08-Gal4 and the PB columnar neurons with R52B10-Gal4 promoted sleep and wakefulness, respectively. A targeted GFP reconstitution across synaptic partners (t-GRASP) analysis demonstrated synaptic contact between these two groups of sleep-regulating PB neurons. Furthermore, we found that activation of a pair of dopaminergic (DA) neurons projecting to the PB (T1 DA neurons) decreased sleep. The wake-promoting T1 DA neurons and the sleep-promoting PB interneurons formed close associations. Dopamine 2-like receptor (Dop2R) knockdown in the sleep-promoting PB interneurons increased sleep. These results indicated that the neuronal circuit in the PB, regulated by dopamine signaling, mediates sleep-wakefulness.

Genes and neural circuits for sleep of the fruit fly.

Sleep is a universal physiological state evolutionarily conserved among species, but the molecular basis for its regulation is still largely unknown. Due to its electroencephalogram criteria, sleep has long been investigated and described mostly in mammalian species. The fruit fly, Drosophila melanogaster, has emerged as a genetic model organism for studying sleep. The Drosophila sleep is behaviorally defined, and is tightly regulated by circadian and homeostatic processes, like mammals. Genetic analyses using Drosophila have successfully identified a number of conserved regulatory mechanisms underlying sleep between flies and mammals. Identification of sleep-regulating neural circuits is required to further elucidate these molecular mechanisms. Two major brain regions, the mushroom bodies and the central complex, play crucial roles in sleep regulation in Drosophila. Noteworthy, many detailed studies on neural circuits in these brain regions have clearly shown that specific small group of neurons are implicated in sleep homeostasis. Thus, recent progress in Drosophila sleep provides novel insights into understanding the molecular and neural basis of sleep.