Metabolic state modulates risky foraging behavior via multiple branches of the insulin/IGF-1-like pathway in <i>C. elegans</i>

Foraging to acquire nutrients is an essential and sometimes risky behavior displayed by nearly all animals. Appropriately balancing foraging risks with nutrient requirements is pivotal for peak survival and reproduction, and metabolic state (i.e., how urgently the animal requires nutrients) is a strong modulator of risky foraging behavior. In this study, we asked what molecular signal allows C. elegans to change its foraging behavior in response to changes in its metabolic state. We used an assay of risky foraging behavior, where wild type worms increase risky foraging behavior after food deprivation, to screen for candidate genes. We found that DAF-2, the singular receptor in the C. elegans insulin/IGF-1 signaling (IIS) pathway, is necessary for worms to modulate risky foraging behavior in response to short-term food deprivation. Worms with mutations in genes upstream and downstream of daf-2 in the IIS pathway also exhibited a reduction in the effect of food deprivation. While a canonical understanding of the IIS pathway would suggest that the FOXO transcription factor DAF-16 is the primary downstream IIS pathway target, we found that DAF-16 was not required for worms to exhibit food-deprivation-driven changes in foraging behavior. Furthermore, we determined that the calsyntenin ortholog CASY-1, which allows DAF-2c to traffic to axons, is required for food deprivation to modulate risky foraging behavior. These results both validate the IIS receptor as a pivotal regulator of risky foraging behavior and suggest a multi-pronged downstream pathway. Overall, these data enrich our understanding of how organisms transduce metabolic state information to make vital decisions about when to engage in risky foraging behaviors.