title: Drosophila Hyperkinetic mutants have reduced sleep and impaired memory.
abstract: In mammals, sleep is thought to be important for health, cognition, and memory. Fruit flies share most features of mammalian sleep, and a recent study found that Drosophila lines carrying loss-of-function mutations in Shaker (Sh) are short sleeping, suggesting that the Sh current plays a major role in regulating daily sleep amount. The Sh current is potentiated by a beta modulatory subunit coded by Hyperkinetic (Hk). Here, we demonstrate that severe loss-of-function mutations of Hk reduce sleep and do so primarily by affecting the Sh current. Moreover, we prove, using a transgenic approach, that a wild-type copy of Hk is sufficient to restore normal sleep. Furthermore, we show that short-sleeping Hk mutant lines have a memory deficit, whereas flies carrying a weaker hypomorphic Hk allele have normal sleep and normal memory. By comparing six short-sleeping Sh lines with two normal sleeping ones, we also found that only alleles that reduce sleep also impair memory. These data identify a gene, Hk, which is necessary to maintain normal sleep, and provide genetic evidence that short sleep and poor memory are linked.
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bushey
authors.forename: Reto
authors.initials: R
authors.lastname: Huber
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
authors.forename: Chiara
authors.initials: C
authors.lastname: Cirelli
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics; D012890:Sleep / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C094813:Hk (hyperkinetic) protein, Drosophila; D015221:Potassium Channels; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels