Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans

Protection of organismal integrity involves both molecular cytoprotective responses and behavioral defenses. Here we show that exposure of Caenorhabditis elegans to high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and aversive behavior. Benzaldehyde preconditioning activates systemic cytoprotective responses involving DAF-16/FOXO, SKN-1/Nrf and Hsp90 in somatic cells, which confer behavioral tolerance to benzaldehyde and cross-tolerance to methyl-salicylate, but not to diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance and does not induce apparent molecular defenses. Reinforcement of the experiences by massed training forms relevant associative memories. Memory retrieval by the odor olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor. Our findings reveal a regulatory link between cytoprotective mechanisms and behavior which facilitates self-protection in real and anticipated stresses and might have relevance in maladaptive avoidant human behaviors.