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The Journal of Neuroscience, May 16, 2007, 27(20):5384-5393; doi:10.1523/JNEUROSCI.0108-07.2007

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Behavioral/Systems/Cognitive
Drosophila Hyperkinetic Mutants Have Reduced Sleep and Impaired Memory

Daniel Bushey, Reto Huber, Giulio Tononi, and Chiara Cirelli

Department of Psychiatry, University of Wisconsin–Madison, Madison, Wisconsin 53719

Correspondence should be addressed to Dr. Chiara Cirelli, Department of Psychiatry, University of Wisconsin–Madison, 6001 Research Park Boulevard, Madison, WI 53719. Email: ccirelli{at}wisc.edu

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 ß 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.

Key words: Drosophila; sleep; learning; memory; Shaker; hyperkinetic

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Received Jan. 10, 2007; revised April 16, 2007; accepted April 16, 2007.

Correspondence should be addressed to Dr. Chiara Cirelli, Department of Psychiatry, University of Wisconsin–Madison, 6001 Research Park Boulevard, Madison, WI 53719. Email: ccirelli{at}wisc.edu

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