Context blindness in the BTBR T+ tf mouse model of autism: impaired contextual control of discrimination reversal learning

Behavioural inflexibility—a hallmark of autism spectrum disorder (ASD)—can be characterised by the persistence of established behaviours in inappropriate contexts. This inflexibility may arise from a reduced ability to use contextual information to disambiguate effective contingencies, thereby impeding the flexible expression of instrumental behaviour in a contextually appropriate manner. In this study, we employed the BTBR T⁺ tf inbred mouse model of ASD to examine whether contextual control of behaviour is impaired in these mice. BTBR and control C57BL/6J (B6) mice were first trained on a T-maze positional discrimination task, after which they were subjected to a reversal task conducted in either the same or a different maze context. The contextual shift significantly facilitated the acquisition of reversal discrimination in B6 mice, whereas it had no effect on BTBR mice. The lack of contextual control resulted in poorer reversal performance in BTBR in the new context, while both strains performed comparably when the context remained unchanged. A subsequent experiment ruled out the possibility that BTBR mice were simply unable to differentiate between the two maze contexts, as they demonstrated normal differential contextual conditioning. Overall, these findings suggest that BTBR mice are critically impaired in utilising contextual cues to disambiguate the effective stimulus–response–outcome contingencies in a hierarchical manner. This supports the notion that “context blindness” is a core deficit in ASD and warrants further investigation into its neurobiological underpinnings.