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

Abstract

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.

Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

“…Therefore, hibernation-linked CREs in the Fto-Irx TAD that influence metabolism could also influence foraging behaviors, as well as age-related foraging changes. To test this in an ethologically-relevant manner, we focused on Fto-Irx::hibE3 -/mice, because they showed the strongest gene expression and metabolic phenotypes, and used an assay and computational ethology approach that we previously developed to study the genetics of naturalistic foraging (50)(51)(52). Our foraging assay includes a foraging arena attached to a home cage (Fig.…”

“…We examine gross foraging behaviors, as well as more fine-grained behaviors uncovered from discrete round trip foraging excursions (Fig. 4B) (50)(51)(52). With this approach, we profiled foraging in male and female Fto-Irx::hibE3 -/and +/+ mice for both young adult (2-3 month old) and aged (12-month old) cohorts.…”

“…4A ). The Exploration phase examines behavior in a novel environment, while the Foraging Phase examines behavior in a now familiar environment, where the mouse expresses perseverative memory responses of the former food patch (Pot2) ( 52 ). During this assay, mice perform many different round-trip foraging excursions from the home ( Fig.…”

“…4D , Movie S1 ). This “second-guessing” memory response is regulated by the synaptic plasticity gene, Arc, demonstrating mechanistic links to learning & memory ( 52 ). As previously described, we examined second-guessing responses in the mice by analyzing the cumulative time spent at the former food patch, Pot2, in 1-min time bins across the 30-minute Foraging phase ( 52 ).…”

“…This “second-guessing” memory response is regulated by the synaptic plasticity gene, Arc, demonstrating mechanistic links to learning & memory ( 52 ). As previously described, we examined second-guessing responses in the mice by analyzing the cumulative time spent at the former food patch, Pot2, in 1-min time bins across the 30-minute Foraging phase ( 52 ). We found a significant interaction between genotype, sex, and age, indicating that Fto-Irx::hibE3 -/- mice exhibit changes to second guessing in age and sex dependent manner.…”