C. elegans aversive olfactory learning generates diverse intergenerational effects

Abstract

Parental experience can modulate the behavior of their progeny. While the molecular mechanisms underlying parental effects or inheritance of behavioral traits have been studied under several environmental conditions, it remains largely unexplored how the nature of parental experience affects the information transferred to the next generation. To address this question, we used C. elegans, a nematode that feeds on bacteria in its habitat. Some of these bacteria are pathogenic and the worm learns to avoid them after a brief exposure. We found, unexpectedly, that a short parental experience increased the preference for the pathogen in the progeny. Furthermore, increasing the duration of parental exposure switched the response of the progeny from attraction to avoidance. To characterize the underlying molecular mechanisms, we found that the RNA-dependent RNA Polymerase (RdRP) RRF-3, required for the biogenesis of 26 G endo-siRNAs, regulated both types of intergenerational effects. Together, we show that different parental experiences with the same environmental stimulus generate different effects on the behavior of the progeny through small RNA-mediated regulation of gene expression.

What can a worm learn in a bacteria-rich habitat?

“…These results suggest that with 4-h exposure the food response elicited by PA14 is significant in the hermaphrodite mothers and that the resulting signals modulate the progeny developing in the uterus. Increasing the duration of PA14 exposure to 8 h enhances the infection to the mothers (Troemel et al, 2006) and reduces the preference for PA14 in the progeny (Pereira et al, 2020). These findings suggest that longer exposure to PA14 induces a stronger response to the pathogenicity of PA14, which changes the response of the progeny to PA14 from attraction to avoidance.…”

“…Because pathogenic bacteria serve as food sources and critical survival constraints to the worm, it is plausible that exposure to the pathogens modulates the nervous system and the behavior of the progenies. A recent study shows that training adult hermaphrodites by feeding on PA14 for 4 h, which is known to produce a robust aversive memory that associates PA14 odorants with virulence in the adult mothers, increases the progeny's preference for the PA14 odorants (Pereira, Gracida, Kagias, & Zhang, 2020). Many animals prefer the food that they are exposed to in utero (Liu & Urban, 2017;Nehring, Kostka, von Kries, & Rehfuess, 2015;Todrank, Heth, & Restrepo, 2011).…”

“…These findings suggest that longer exposure to PA14 induces a stronger response to the pathogenicity of PA14, which changes the response of the progeny to PA14 from attraction to avoidance. While 4 to 8-h parental training with PA14 produces robust aversive memory in the hermaphrodite mothers, their modulatory effects on the progeny are limited to the first generation of the offspring (Pereira et al, 2020).…”

“…Further increasing the duration of PA14 exposure to 24 h that starts at the L4 larval stage not only generates avoidance of PA14 in the exposed mothers, but also produces PA14 avoidance in the progeny for 4 generations through a separate mechanism (Moore et al, 2019). However, both the effect of 4-h training on the progeny and the multi-generational effect require the endo-RNAi pathway and the piRNA pathway (Moore et al, 2019;Pereira et al, 2020). Small RNA pathways also mediate olfactory adaptation by regulating the expression of genes critical for odorant sensation (Juang et al, 2013).…”

Bacterial small RNAs and host epigenetic effectors of a transgenerational memory of pathogens in C. elegans

“…For instance, worms identify pathogens based on their smell and learn to avoid them (Zhang, Lu, & Bargmann, 2005). Attractive or repulsive odors can also generate long-lasting heritable memory (Remy, 2010;Moore, Kaletsky, & Murphy, 2019;Pereira, Gracida, Kagias, & Zhang, 2020). To avoid infection in the absence of food alternatives, part of the progeny of pathogen-fed nematodes undergoes Pathogen-Induced Diapause Formation (PIDF), as a survival strategy for the collective (Palominos et al, 2017;Gabaldón et al, 2020).…”