Arc Regulates a “Second-Guessing” Cognitive Bias During Naturalistic Foraging

Foraging involves innate decision heuristics that are adapted for the wild but can cause economically irrational cognitive biases in some contexts. The mechanisms underlying cognitive biases are poorly understood but likely involve genetic mechanisms. Here, we investigate foraging in fasted mice using a naturalistic paradigm and uncover an innate “second-guessing” cognitive bias that involves repeatedly investigating a former depleted food patch instead of consuming available food. Second-guessing is economically irrational because it incurs energetic costs in place of caloric benefits. Since learning and memory are involved, we tested roles for Arc and found that Arc-/- mice lack second-guessing, which causes increased food consumption in males during foraging. Using unsupervised machine learning, decompositions of Arc-/- and +/+ mouse behavior show that Arc affects discrete foraging sequences involved in second-guessing and later stages of memory. Thus, revealing a genetic basis for this bias and ethological role for Arc in a naturalistic behavior.