C. elegans worms exhibit a natural chemotaxis towards food cues. This provides a potential platform to study the interactions between stimulus valence and innate behavioral preferences. Here we perform a comprehensive set of choice assays to measure worms’ relative preference towards various attractants. Surprisingly, we find that when facing a combination of choices, worms’ preferences do not always follow value-based hierarchy. In fact, the innate chemotaxis behavior in worms robustly violates key rationality paradigms of transitivity, independence of irrelevant alternatives and regularity. These violations arise due to asymmetric modulatory effects between the presented options. Functional analysis of the entire chemosensory system at a single-neuron resolution, coupled with analyses of mutants, defective in individual neurons, reveals that these asymmetric effects originate in specific sensory neurons.

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.

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 four types of associative memories (short- and long-term memories, each as positive and negative associations) are encoded within the compact neural network of Caenorhabditis elegans worms. Interestingly, sensory neurons were primarily involved in coding short-term, but not long-term, memories, and individual sensory neurons could be assigned to coding either the conditioned stimulus or the experience valence (or both). Moreover, when considering the collective activity of the sensory neurons, the specific training experiences could be decoded. Interneurons integrated the modulated sensory inputs and a simple linear combination model identified the experience-specific modulated communication routes. The widely distributed memory suggests that integrated network plasticity, rather than changes to individual neurons, underlies the fine behavioral plasticity. This comprehensive study reveals basic memory-coding principles and highlights the central roles of sensory neurons in memory formation.

Experiences have been shown to modulate behavior and physiology of future generations in some contexts, but there is limited evidence for inheritance of associative memory in different species. Here, we trained C. elegans nematodes to associate an attractive odorant with stressful starvation conditions and revealed that this associative memory was transmitted to the F1 progeny who showed odor-evoked avoidance behavior. Moreover, the F1 and the F2 descendants of trained animals exhibited odor-evoked cellular stress responses, manifested by the translocation of DAF-16/FOXO to cells’ nuclei. Sperm, but not oocytes, transmitted these odor-evoked cellular stress responses which involved H3K9 and H3K36 methylations, the small RNA pathway machinery, and intact neuropeptide secretion. 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. Moreover, inheritance of the cellular stress responses increased survival chances of the progeny as exposure to the training odorant allowed the animals to prepare in advance for an impending adversity. These findings suggest that in C. elegans associative memories and cellular changes may be transferred across generations.

Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatiotemporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron in Caenorhabditis elegans animals can cell‐autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly changing continuous gradients. This encoding relies on a simple negative feedback in the G‐protein‐coupled receptor (GPCR) signaling pathway in which TAX‐6/Calcineurin plays a key role in mediating the feedback inhibition. This negative feedback supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradient's first derivative. A simple mathematical model explains the fine neural dynamics of both wild‐type and tax‐6 mutant animals, further highlighting how the calcium‐dependent activity of TAX‐6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a general solution for efficient cell‐autonomous coding of external stimuli.