The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster

PLoS One. 2015 May 29;10(5):e0128101. doi: 10.1371/journal.pone.0128101. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Brain / metabolism
  • Brain / pathology
  • Dizocilpine Maleate / pharmacology
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Monoiodotyrosine / pharmacology
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sleep / genetics
  • Sleep / physiology*

Substances

  • 3-iodotyrosine
  • Drosophila Proteins
  • NMDA receptor A1
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Monoiodotyrosine

Associated data

  • GEO/GSE56149

Grants and funding

This research was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) (22300132, 25290007, K.K., 22700433, 24700413, J.T.). T.U. was supported by Grant-in-Aid for JSPS Fellows.