Variable behavior and repeated learning in two mouse strains: Developmental and genetic contributions.

Behavioral inflexibility is often assessed using reversal learning tasks, which require a relatively low degree of response variability. No studies have assessed sensitivity to reinforcement contingencies that specifically select highly variable response patterns in mice, let alone in models of neurodevelopmental disorders involving limited response variation. Operant variability and incremental repeated acquisition (IRA) were used to assess unique aspects of behavioral variability of two mouse strains: BALB/c, a model of some deficits in ASD, and C57Bl/6. On the operant variability task, BALB/c mice responded more repetitively during adolescence than C57Bl/6 mice when reinforcement did not require variability but responded more variably when reinforcement required variability. During IRA testing in adulthood, both strains acquired an unchanging, performance sequence equally well. Strain differences emerged, however, after novel learning sequences began alternating with the performance sequence: BALB/c mice substantially outperformed C57Bl/6 mice. Using litter-mate controls, it was found that adolescent experience with variability did not affect either learning or performance on the IRA task in adulthood. These findings constrain the use of BALB/c mice as a model of ASD, but once again reveal this strain is highly sensitive to reinforcement contingencies and they are fast and robust learners.