A gut-secreted peptide suppresses arousability from sleep

Cell. 2023 Mar 30;186(7):1382-1397.e21. doi: 10.1016/j.cell.2023.02.022. Epub 2023 Mar 22.


Suppressing sensory arousal is critical for sleep, with deeper sleep requiring stronger sensory suppression. The mechanisms that enable sleeping animals to largely ignore their surroundings are not well understood. We show that the responsiveness of sleeping flies and mice to mechanical vibrations is better suppressed when the diet is protein rich. In flies, we describe a signaling pathway through which information about ingested proteins is conveyed from the gut to the brain to help suppress arousability. Higher protein concentration in the gut leads to increased activity of enteroendocrine cells that release the peptide CCHa1. CCHa1 signals to a small group of dopamine neurons in the brain to modulate their activity; the dopaminergic activity regulates the behavioral responsiveness of animals to vibrations. The CCHa1 pathway and dietary proteins do not influence responsiveness to all sensory inputs, showing that during sleep, different information streams can be gated through independent mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal* / physiology
  • Biological Transport
  • Brain / metabolism
  • Intestines / metabolism
  • Mice
  • Peptides / metabolism
  • Peptides / pharmacology
  • Sleep* / physiology


  • Peptides