Insulin Signaling Plays a Dual Role in Caenorhabditis elegans Memory Acquisition and Memory Retrieval

Insulin signaling plays a prominent role in regulation of dauer formation and longevity in Caenorhabditis elegans. Here, we show that insulin signaling also is required in benzaldehyde-starvation associative plasticity, in which worms pre-exposed to the odor attractant benzaldehyde in the absence of food subsequently demonstrate a conditioned aversion response toward the odorant. Animals with mutations in insulin-related 1 (ins-1), abnormal dauer formation 2 (daf-2), and aging alteration 1 (age-1), which encode the homolog of human insulin, insulin/IGF-1 receptor, and PIP3 kinase, respectively, demonstrated significant deficits in benzaldehyde-starvation associative plasticity. Using a conditional allele, we show that the behavioral roles of DAF-2 signaling in associative plasticity can be dissociated, with DAF-2 signaling playing a more significant role in the memory retrieval than in memory acquisition. We propose DAF-2 signaling acts as a learning-specific starvation signal in the memory acquisition phase of benzaldehyde-starvation associative plasticity but functions to switch benzaldehyde-sensing amphid wing C neurons into an avoidance signaling mode during memory retrieval.