title: The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster.
abstract: Considerable evidence indicates that sleep is essential for learning and memory. Drosophila melanogaster has emerged as a novel model for studying sleep. We previously found a short sleeper mutant, fumin (fmn), and identified its mutation in the dopamine transporter gene. We reported similarities in the molecular basis of sleep and arousal regulation between mammals and Drosophila. In aversive olfactory learning tasks, fmn mutants demonstrate defective memory retention, which suggests an association between sleep and memory. In an attempt to discover additional sleep related genes in Drosophila, we carried out a microarray analysis comparing mRNA expression in heads of fmn and control flies and found that 563 genes are differentially expressed. Next, using the pan-neuronal Gal4 driver elav-Gal4 and UAS-RNA interference (RNAi) to knockdown individual genes, we performed a functional screen. We found that knockdown of the NMDA type glutamate receptor channel gene (Nmdar1) (also known as dNR1) reduced sleep. The NMDA receptor (NMDAR) plays an important role in learning and memory both in Drosophila and mammals. The application of the NMDAR antagonist, MK-801, reduced sleep in control flies, but not in fmn. These results suggest that NMDAR promotes sleep regulation in Drosophila.
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Tomita
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Mitsuyoshi
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors.forename: Shoen
authors.initials: S
authors.lastname: Kume
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kume
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007470:Monoiodotyrosine / Q000494:pharmacology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012890:Sleep / Q000235:genetics / Q000502:physiology*
chemical_list: D016291:Dizocilpine Maleate; D029721:Drosophila Proteins; D007470:Monoiodotyrosine; D016194:Receptors, N-Methyl-D-Aspartate; C523964:3-iodotyrosine