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

Abstract

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.

Two Forms of Learning following Training to a Single Odorant in Caenorhabditis elegans AWC Neurons

“…Similarly, we could completely rescue IsoA3 Bnz adaptation in an age-1 mutant with expression of age-1 in the AWC (Fig. 4d), despite the fact that worms were trained to a different odorant than in the Bnz3 Bnz learning reported by Lin et al (2010). These results strengthen the suggestion that IsoA3 Bnz and Bnz3 Bnz represent the same memory trace, one that is distinct from that sampled in the IsoA3 IsoA protocol.…”

“…A number of genes have been implicated in AWC adaptation, including members of the insulin signaling pathway (Chalasani et al, 2010;Lin et al, 2010), the transient receptor potential type V (TRPV) channel osm-9 (Colbert et al, 1997), the cGMPdependent kinase egl-4 (L' Etoile et al, 2002), the arrestin arr-1 (Palmitessa et al, 2005), and the guanalyl cyclase gcy-28 (Tsuno-zaki et al, 2008). We therefore mimicked the approach of Atkinson-Leadbeater et al (2004), instead analyzing candidate genes to assign them to specific components (acquisition or retrieval) or types (habituation or associative learning) of memory.…”

“…al., 2010; Lin et al, 2010). By using a conditional allele of the C. elegans insulin receptor homolog abnormal dauer formation 2 (daf-2), our previous work (Lin et al, 2010) demonstrated that insulin signaling was only partially required during training, but absolutely essential during memory retrieval processes of Bnz3 Bnz associative learning.…”

“…That is, ins-1 dependence is entirely correlated with food and serotonin sensitivity. We have previously shown that a strain carrying a temperature-sensitive conditional allele of the insulin receptor, daf-2(e1370), demonstrates a complete adaptation deficit in Bnz3 Bnz adaptation when tested at the nonpermissive temperature (Lin et al, 2010). We therefore tested daf-2(e1370) in each of the adaptation protocols at the nonpermissive temperature (Fig.…”

“…Bonferroni's corrections revealed a significant difference for the IsoA3 IsoA and Bnz3 IsoA experimental protocols. Lin et al (2010) suggested that function of the insulin pathway in the AWC sensory neuron itself was sufficient to rescue Bnz3 Bnz associative learning in an insulin pathway mutant, age-1(hx546), background. Similarly, we could completely rescue IsoA3 Bnz adaptation in an age-1 mutant with expression of age-1 in the AWC (Fig.…”