FMRFamide signaling promotes stress-induced sleep in Drosophila

Brain Behav Immun. 2015 Jul;47:141-8. doi: 10.1016/j.bbi.2014.12.028. Epub 2015 Feb 7.


Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress.

Keywords: Circadian rhythms; Drosophila; Neurogenetics; Neuropeptides; Sleep; Stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila
  • FMRFamide / genetics
  • FMRFamide / metabolism*
  • Hot Temperature
  • Receptors, Invertebrate Peptide / genetics
  • Receptors, Invertebrate Peptide / metabolism*
  • Signal Transduction
  • Sleep / physiology*
  • Stress, Physiological / physiology*


  • FMRFamide receptor
  • Receptors, Invertebrate Peptide
  • FMRFamide