Reduced sleep in Drosophila Shaker mutants

Abstract

Most of us sleep 7-8 h per night, and if we are deprived of sleep our performance suffers greatly; however, a few do well with just 3-4 h of sleep-a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. To do so, we performed mutagenesis in Drosophila melanogaster, because flies also sleep for many hours and, when sleep deprived, show sleep rebound and performance impairments. By screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for one-third of the wild-type amount. We show that mns flies perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation. We then show that mns flies carry a point mutation in a conserved domain of the Shaker gene. Moreover, after crossing out genetic modifiers accumulated over many generations, other Shaker alleles also become short sleepers and fail to complement the mns phenotype. Finally, we show that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency.

IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Neuronal Firing in the Suprachiasmatic Nucleus and Circadian Rhythms in Locomotor Activity

“…Because the durations in daily firing patterns in SCN neurons deficient for Kv1.4 were not significantly different from WT SCN neurons, the behavioral phenotype may result from the functioning of Kv1.4-encoded I A channels outside the SCN. Together with previous studies linking Kv channel functioning to sleep in mice and in flies (Vyazovskiy et al, 2002;Cirelli et al, 2005;Douglas et al, 2007;Espinosa et al, 2008;Koh et al, 2008), the results here support the interesting possibility that modulation of Kv channels (and other conductances that regulate intrinsic neuronal excitability) play critical roles in both circadian biology and sleep.…”

Day–night cycles and the sleep-promoting factor, Sleepless, affect stem cell activity in the Drosophila testis

“…The apparent loss of rhythms may be caused by the overall increased rate of divisions. The other mutants tested here do not have sleep phenotypes as extreme as the reduction of sleep in sss mutants (23)(24)(25)(26), which may account for the maintenance of normal stem cell activity in these flies. However, it is possible that some sleep-regulating pathways also regulate stem cell activity, whereas others do not.…”

“…altered (Fig. 3A), presumably because of their less severe sleep phenotypes (23)(24)(25)(26). Alternatively, SSS may modulate stem cell divisions through mechanisms unrelated to its function in sleep, or the sleep-regulating pathways affected in sss flies may be different from the pathways altered in other sleep mutants (discussed below).…”

“…2) and iso31 strains (controls and genetic background in Figs. 3 and 4) (Bloomington Stock Center), sss P1 (23), DAT fumin (24), shaker gene locus (25), gabat PL (provided by W.-F.C. ), elav-GeneSwitch (51), elav-Gal4 (Bloomington Stock Center), UAS-mc* (52), and UAS-sss (27) strains.…”

Identification of a biomarker for sleep drive in flies and humans

“…For example, genetic studies have begun to identify mutations in humans, mice, and flies that alter sleep time and sleep homeostasis (27)(28)(29)(30). Similarly, ethological studies have reported instances where animals can sustain waking for extended periods of time without exhibiting a homeostatic response [e.g., cetacean (31) and white-crown sparrow (32)].…”