Identifying sleep regulatory genes using a Drosophila model of insomnia

Laurent Seugnet, Yasuko Suzuki, Matthew Thimgan, Jeff Donlea, Sarah I. Gimbel, Laura Gottschalk, Steve P. Duntley, Paul J. Shaw

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Although it is widely accepted that sleep must serve an essential biological function, little is known about molecules that underlie sleep regulation. Given that insomnia is a common sleep disorder that disrupts the ability to initiate and maintain restorative sleep, a better understanding of its molecular underpinning may provide crucial insights into sleep regulatory processes. Thus, we created a line of flies using laboratory selection that share traits with human insomnia. After 60 generations, insomnia-like (ins-l) flies sleep 60 min a day, exhibit difficulty initiating sleep, difficulty maintaining sleep, and show evidence of daytime cognitive impairment. ins-l flies are also hyperactive and hyperresponsive to environmental perturbations. In addition, they have difficulty maintaining their balance, have elevated levels of dopamine, are short-lived, and show increased levels of triglycerides, cholesterol, and free fatty acids. Although their core molecular clock remains intact, ins-l flies lose their ability to sleep when placed into constant darkness. Whole-genome profiling identified genes that are modified in ins-l flies. Among those differentially expressed transcripts, genes involved in metabolism, neuronal activity, and sensory perception constituted over-represented categories. We demonstrate that two of these genes are upregulated in human subjects after acute sleep deprivation. Together, these data indicate that the ins-l flies are a useful tool that can be used to identify molecules important for sleep regulation and may provide insights into both the causes and long-term consequences of insomnia.

Original languageEnglish
Pages (from-to)7148-7157
Number of pages10
JournalJournal of Neuroscience
Issue number22
StatePublished - Jun 3 2009


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