The 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.

A major goal in neuroscience is to elucidate the principles by which memories are stored in a neural network. Here, we have systematically studied how the four types of associative memories (short- and long-term memories, each formed using positive and negative associations) are encoded within the compact neural network of C. elegans worms. Interestingly, short-term, but not long-term, memories are evident in the sensory system. Long-term memories are relegated to inner layers of the network, allowing the sensory system to resume innate functionality. Furthermore, a small set of sensory neurons is allocated for coding short-term memories, a design that can increase memory capacity and limit non-innate behavioral responses. Notably, individual sensory neurons may code for the conditioned stimulus or the experience valence. Interneurons integrate these information to modulate animal behavior upon memory reactivation. This comprehensive study reveals basic principles by which memories are encoded within a neural network, and highlights the central roles of sensory neurons in memory formation.

Organisms’ capacity to anticipate future conditions is key for survival. Associative memories are instrumental for learning from past experiences, yet little is known about the processes that follow memory retrieval and their potential advantage in preparing for impending developments. Here, using C. elegans nematodes, we demonstrate that odor-evoked retrieval of aversive memories induces rapid and protective stress responses, which increase animal survival prospects when facing imminent adversities. The underlying mechanism relies on two sensory neurons: one is necessary during the learning period, and the other is necessary and sufficient for memory retrieval. Downstream of memory reactivation, serotonin secreted from two head neurons mediates the systemic stress response. Thus, evoking stressful memories, stored within individual sensory neurons, allows animals to anticipate upcoming dire conditions and provides a head start to initiate rapid and protective responses that ultimately increase animal fitness. Anticipating future adversities is key for animals’ survival. Eliezer et al. show that, following reactivation of a stressful memory, C. elegans worms can anticipate harsh conditions and prepare for them in advance. This process relies on one neuron that is important for learning, and another that is necessary and sufficient for memory retrieval.

The ability of animals to effectively locate and navigate toward food sources is central for survival. Here, using C. elegans nematodes, we reveal the neural mechanism underlying efficient navigation in chemical gradients. This mechanism relies on the activity of two types of chemosensory neurons: one (AWA) coding gradients via stochastic pulsatile dynamics, and the second (AWCON) coding the gradients deterministically in a graded manner. The pulsatile dynamics of the AWA neuron adapts to the magnitude of the gradient derivative, allowing animals to take trajectories better oriented toward the target. The robust response of AWCON to negative derivatives promotes immediate turns, thus alleviating the costs incurred by erroneous turns dictated by the AWA neuron. This mechanism empowers an efficient navigation strategy that outperforms the classical biased-random walk strategy. This general mechanism thus may be applicable to other sensory modalities for efficient gradient-based navigation.