Ingestion of contaminated food can cause nausea, retching and, in some species, vomiting. Writing in Cell, Cao and colleagues describe a gut–brain pathway that mediates such toxin-induced defensive responses in mice. Intraperitoneal injection of staphylococcal enterotoxin A (SEA) — which causes food poisoning in humans — triggered retching-like mouth-opening responses and induced conditioned flavour aversion (CFA, thought to reflect nausea) in mice. These responses were inhibited by NK1R or 5HT3R antagonists and by vagotomy, and the authors provide evidence that 5-HT synthesis in enteroendocrine cells signals to vagal sensory neurons, which target the dorsal vagal complex (DVC). SEA injection caused activation of Tac1-expressing DVC neurons that immediately preceded the retching-like behaviour and CFA. Further experiments indicated that activation of these neurons, and their expression of Tac1 and Slc17a6, regulate SEA-triggered behavioural responses. The authors also showed that projections from Tac1+ DVC neurons to the ventral respiratory group (VRP) and the lateral parabrachial nucleus (LPB) are selectively required for SEA-induced retching-like behaviour and CFA, respectively. Interestingly, SEA did not activate enteroendocrine cells directly, and the authors propose that a previously described SEA-induced inflammatory response in the gastrointestinal tract induces 5HT release to set off this pathway.
