Hunger or thirst state uncertainty is resolved by outcome evaluation in medial prefrontal cortex to guide decision-making

Eiselt et al. report conditions under which mice confuse thirst for hunger, similar to some human decisions that lead to over-eating. Evaluation of physiological need state requires consuming food or water and depends on the prefrontal cortex. Physiological need states direct decision-making toward re-establishing homeostasis. Using a two-alternative forced choice task for mice that models elements of human decisions, we found that varying hunger and thirst states caused need-inappropriate choices, such as food seeking when thirsty. These results show limits on interoceptive knowledge of hunger and thirst states to guide decision-making. Instead, need states were identified after food and water consumption by outcome evaluation, which depended on the medial prefrontal cortex.