title: Kynurenic acid is a nutritional cue that enables behavioral plasticity.
abstract: 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.
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158-2240, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Lemieux
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158-2240, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Cunningham
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158-2240, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158-2240, USA.
authors.forename: Fahima
authors.initials: F
authors.lastname: Mayer
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, CA 94158-2240, USA. Electronic address: kaveh.ashrafi@ucsf.edu.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Ashrafi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000378:metabolism*; D003463:Cues; D005215:Fasting; D005247:Feeding Behavior; D007395:Interneurons / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012701:Serotonin; D015398:Signal Transduction; D000637:Transaminases / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D007737:Kynurenine; D014364:Tryptophan; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D007736:Kynurenic Acid