Learning of pathogenic bacteria in adult C. elegans bidirectionally regulates pathogen response in the progeny

Parental experience can generate adaptive changes in the behavioral and physiological traits of the offspring. However, the biological properties of this intergenerational regulation and the underlying molecular and cellular mechanisms are not well understood. Here, we show that the experience of learning to avoid pathogenic bacteria in C. elegans alters the behavioral response to the pathogen in the progeny through the endogenous RNA interference (RNAi) pathway. We previously show that the adult C. elegans learns to avoid the smell of pathogenic bacteria, such as the Pseudomonas aeruginosa strain PA14, after feeding on the pathogen for a few hours. Here, we report that this learning experience can bidirectionally regulate the olfactory response to PA14 in the progeny that are never directly exposed to the pathogen. The olfactory preference for PA14 in these progeny is linearly correlated with the learned avoidance of PA14 in their mothers. If the mothers show strong learning of PA14, their progeny avoid PA14; intriguingly, if the mothers show weak learning of PA14, the progeny prefer PA14, suggesting that the PA14-trained mothers transmit both the negative and positive information of PA14 to their progeny. The intergenerational behavioral effect results from an altered behavioral decision regulated by an olfactory sensorimotor neural circuit. Learning to avoid the pathogen also influences the development of the progeny, which is regulated independently from the behavioral change. Animals mutated for the RRF-3/RNA-directed RNA polymerase, a master regulator for the synthesis of the small interfering RNAs that are maternally inherited or in the soma, display the normal naive and learned response to PA14 but are defective in regulating the olfactory response to PA14 in their progeny. Our results characterize an intergenerational effect that allows the progeny to rapidly adapt to an environmental condition that is critical for survival.