Genetic background and reversal learning: differences in behavioral flexibility between CD1 and C57BL/6 strains in...

Reversal learning is the ability to modify responses based on changes in stimulus-outcome contingencies. Behavioral flexibility is crucial for adaptive behavior in dynamic environments, where organisms must suppress previously acquired responses and adopt new strategies to survive. In this study, we compared two mouse strains: C57BL/6 (inbred) mice, which offer genetic uniformity, and CD1 (outbred) mice, providing genetic diversity. Mice were tested in the mid-session reversal (MSR) task under three conditions: fixed reversal with 100% reinforcement (F100), variable reversal with 100% reinforcement (V100), and variable reversal with 50% reinforcement (V50). To account for prior experience, phases 1 and 2 were counterbalanced across subjects. Both strains completed the MSR task but showed distinct response profiles. CD1 mice showed consistent adaptation across reversal conditions (F100 and V100), maintaining high accuracy. Under reduced reinforcement predictability (V50), both strains showed increased variability, indicating diminished stimulus control. Individuals from both strains employ a mix of win-stay/lose-shift (WSLS) and temporal strategies; however, these do not always yield optimal results, indicating that their responses are driven by a blend of tactics rather than fixed rules. Notably, the order of conditions had a greater effect on C57BL/6 mice, suggesting increased sensitivity to task order. These findings highlight the influence of genetic background and reinforcement structure on reversal learning. Strain-specific profiles should be considered when selecting models for research on cognitive flexibility, reinforcement sensitivity, and translational studies related to decision-making under uncertainty.