Arc Regulates a Second-Guessing Cognitive Bias During Naturalistic Foraging Through Effects on Discrete Behavior Modules

Foraging involves innate decision heuristics that are adapted for the wild but can cause economically suboptimal cognitive biases in some contexts. The mechanisms underlying cognitive biases are poorly understood but are likely genetic. Here, we investigate foraging in fasted mice using a naturalistic paradigm and uncover an innate "second-guessing" cognitive bias that involves repeatedly investigating an empty former food patch instead of consuming available food. Second-guessing prevents mice from maximizing feeding benefits in the task. Since learning and memory are involved, we tested roles for the synaptic plasticity gene, Arc, and found that Arc-/- mice show a specific lack of second-guessing. Arc-/- males reap benefits by increasing food consumption. Unsupervised machine learning decompositions of foraging show that Arc affects discrete, stereotyped foraging sequences that we call modules within a rich naturalistic behavioral landscape. Thus, our study reports a second- guessing cognitive bias, ethological roles for Arc in naturalistic foraging, and links between genetically determined foraging modules and cognitive bias in decision making.