A brainstem circuit for nausea suppression

Cell Rep. 2022 Jun 14;39(11):110953. doi: 10.1016/j.celrep.2022.110953.


Nausea is a discomforting sensation of gut malaise that remains a major clinical challenge. Several visceral poisons induce nausea through the area postrema, a sensory circumventricular organ that detects bloodborne factors. Here, we use genetic approaches based on an area postrema cell atlas to reveal inhibitory neurons that counteract nausea-associated poison responses. The gut hormone glucose insulinotropic peptide (GIP) activates area postrema inhibitory neurons that project locally and elicit inhibitory currents in nausea-promoting excitatory neurons through γ-aminobutyric acid (GABA) receptors. Moreover, GIP blocks behavioral responses to poisons in wild-type mice, with protection eliminated by targeted area postrema neuron ablation. These findings provide insights into the basic organization of nausea-associated brainstem circuits and reveal that area postrema inhibitory neurons are an effective pharmacological target for nausea intervention.

Keywords: CP: Neuroscience; GDF15; GFRAL; GIPR; channelrhodopsin-assisted circuit mapping; circumventricular organ; conditioned flavor avoidance; growth/differentiation factor 15; sickness behavior.

Publication types

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

MeSH terms

  • Animals
  • Area Postrema* / physiology
  • Brain Stem
  • Mice
  • Nausea
  • Neurons / physiology
  • Poisons* / pharmacology


  • Poisons