Neuromedin U signaling regulates memory retrieval of learned salt avoidance in aC. elegansgustatory circuit

AbstractLearning and memory are regulated by neuromodulatory pathways, but the contribution and temporal requirement of most neuromodulators in a learning circuit are unknown. Here we identify the evolutionarily conserved neuromedin U (NMU) neuropeptide family as a regulator of memory retrieval inC. elegansgustatory aversive learning. The NMU homolog CAPA-1 and its receptor NMUR-1 are required for the expression of learned salt avoidance. Aversive learning depends on the release of CAPA-1 neuropeptides from sensory ASG neurons that respond to salt stimuli in an experience-dependent manner. Optogenetic silencing of CAPA-1 neurons blocks the immediate retrieval, but not the acquisition, of learned salt avoidance. CAPA-1 subsequently signals through NMUR-1 in AFD sensory neurons to modulate two navigational strategies for salt chemotaxis. Aversive conditioning thus recruits NMU signaling to eventually modulate locomotor programs for expressing learned avoidance behavior. Because NMU signaling is conserved across bilaterian animals, our findings incite further research into its function in other memory and decision-making circuits.Graphical Abstract