Inheritance of associative memories inC. elegansnematodes

Abstract

SummaryThe notion that associative memories may be transmitted across generations is intriguing, yet controversial. Here, we trained C. elegans nematodes to associate an odorant with stressful starvation conditions, and surprisingly, this associative memory was evident two generations down of the trained animals. The inherited memory endowed the progeny with a fitness advantage, as memory reactivation induced rapid protective stress responses that allowed the animals to prepare in advance for an impending adversity. Sperm, but not oocytes, transmitted the associative memory, and the inheritance required H3K9 and H3K36 methylations, the small RNA-binding Argonaute NRDE-3, and intact neuropeptide secretion. Remarkably, activation of a single chemosensory neuron sufficed to induce a serotonin-mediated systemic stress response in both the parental trained generation and in its progeny. These findings challenge long-held concepts by establishing that associative memories may indeed be transferred across generations.

Small RNAs Worm Up Transgenerational Epigenetics Research

“…Based on genetic analyses in different experimental systems, the heritable biological responses to environmental changes appear to rely both on dsRNA transport from the soma to the germline [ 73 ] and on germline TEI driven by piRNAs and/or siRNA amplification [ 69 , 70 , 72 , 73 ]. Most recently, Zaslaver and colleagues designed C. elegans training experiments inducing an associative memory between an odorant and starvation, which was monitored via nuclear translocation of a global stress response factor upon memory reactivation [ 74 ]. Remarkably, this association persisted in the progeny of trained worms for two generations and required both RNAi and chromatin regulators [ 74 ].…”

“…Most recently, Zaslaver and colleagues designed C. elegans training experiments inducing an associative memory between an odorant and starvation, which was monitored via nuclear translocation of a global stress response factor upon memory reactivation [ 74 ]. Remarkably, this association persisted in the progeny of trained worms for two generations and required both RNAi and chromatin regulators [ 74 ].…”