biostudies-literatureLemieux GANIDDK NIH HHSNIA NIH HHSNIEHS NIH HHSNIH HHS119-31https://www.ebi.ac.uk/biostudies/studies/S-EPMC4334586biostudies-literatureUnknown160(1-2)The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases, but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food-dependent behavioral plasticity in C. elegans. The experience of fasting in C. elegans alters a variety of behaviors, including feeding rate, when food is encountered post-fast. Levels of neurally produced kynurenic acid are depleted by fasting, leading to activation of NMDA-receptor-expressing interneurons and initiation of a neuropeptide-y-like signaling axis that promotes elevated feeding through enhanced serotonin release when animals re-encounter food. Upon refeeding, kynurenic acid levels are eventually replenished, ending the elevated feeding period. Because tryptophan is an essential amino acid, these findings suggest that a physiological role of kynurenic acid is in directly linking metabolism to activity of NMDA and serotonergic circuits, which regulate a broad range of behaviors and physiologies.CellKynurenic acid is a nutritional cue that enables behavioral plasticity.PMC4334586P30 DK063720U01 ES019458R21 ES021412U01ES019458P40 OD010440R01 AG046400Werb ZCunningham KAMayer FLemieux GALin LAshrafi KfalseKynurenic acid is a nutritional cue that enables behavioral plasticity.The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases, but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food-dependent behavioral plasticity in C. elegans. The experience of fasting in C. elegans alters a variety of behaviors, including feeding rate, when food is encountered post-fast. Levels of neurally produced kynurenic acid are depleted by fasting, leading to activation of NMDA-receptor-expressing interneurons and initiation of a neuropeptide-y-like signaling axis that promotes elevated feeding through enhanced serotonin release when animals re-encounter food. Upon refeeding, kynurenic acid levels are eventually replenished, ending the elevated feeding period. Because tryptophan is an essential amino acid, these findings suggest that a physiological role of kynurenic acid is in directly linking metabolism to activity of NMDA and serotonergic circuits, which regulate a broad range of behaviors and physiologies.2015-01-01T00:00:00Z2015 Jan2025-05-29T21:21:56.078Z2025-05-29T21:21:56.078ZS-EPMC43345862559417710.1016/j.cell.2014.12.028