The NMDA Receptor Promotes Sleep in the Fruit Fly, <i>Drosophila melanogaster</i>

<div><p>Considerable evidence indicates that sleep is essential for learning and memory. <i>Drosophila melanogaster</i> has emerged as a novel model for studying sleep. We previously found a short sleeper mutant, <i>fumin</i> (<i>fmn</i>), and identified its mutation in the dopamine transporter gene. We reported similarities in the molecular basis of sleep and arousal regulation between mammals and <i>Drosophila</i>. In aversive olfactory learning tasks, <i>fmn</i> mutants demonstrate defective memory retention, which suggests an association between sleep and memory. In an attempt to discover additional sleep related genes in <i>Drosophila</i>, we carried out a microarray analysis comparing mRNA expression in heads of <i>fmn</i> and control flies and found that 563 genes are differentially expressed. Next, using the pan-neuronal <i>Gal4</i> driver <i>elav</i>-<i>Gal4 and UAS</i>-RNA interference (RNAi) to knockdown individual genes, we performed a functional screen. We found that knockdown of the NMDA type glutamate receptor channel gene (<i>Nmdar1</i>) (also known as <i>dNR1</i>) reduced sleep. The NMDA receptor (NMDAR) plays an important role in learning and memory both in <i>Drosophila</i> and mammals. The application of the NMDAR antagonist, MK-801, reduced sleep in control flies, but not in <i>fmn</i>. These results suggest that NMDAR promotes sleep regulation in <i>Drosophila</i>.</p>