Neuromedin U signaling regulates memory retrieval of learned salt avoidance in a C. elegans gustatory circuit

Abstract

Learning 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 in C. elegans gustatory 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.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC=\"FIGDIR/small/683888v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (58K):\norg.highwire.dtl.DTLVardef@10bf862org.highwire.dtl.DTLVardef@dfeb7eorg.highwire.dtl.DTLVardef@dda0b8org.highwire.dtl.DTLVardef@62bc95_HPS_FORMAT_FIGEXP M_FIG C_FIG