Dissociable control of persistence and adaptive updating in reward-guided behavior

Adaptive behavior requires a balance between persistence and flexibility, whereas excessive persistence and impaired updating characterize several neuropsychiatric disorders. Touchscreen-based cognitive tasks provide a reverse-translational framework because closely related visual-discrimination and reversal paradigms are used to phenotype cognitive flexibility in rodents and humans. Here, we examined the role of the melanin-concentrating hormone (MCH) system using appetitive touchscreen extinction and reversal tasks. Blocking MCHR1 had little effect while an established reward contingency remained valid, but facilitated behavioral adaptation when reinforcement was withdrawn or reversed. These findings suggest that MCHR1 signaling promotes persistence of previously reinforced behavior. We then chemogenetically activated lateral hypothalamic MCH neurons. Activation produced no detectable change in extinction, but altered learning during reversal. Notably, behavioral differences were also evident during a subsequent reversal performed without chemogenetic activation: mice previously exposed to MCH-neuron activation learned the new contingency more rapidly, yet showed greater persistence after individual errors. Thus, MCHR1 blockade and MCH-neuron activation affect distinct components of behavioral updating rather than producing simple opposite effects. Together, these findings identify dissociable MCH-system contributions to reward-contingency updating in a behavioral framework directly relevant to cross-species neuropsychiatric research.