Dissociable roles of the medial prefrontal cortex, the anterior cingulate cortex, and the hippocampus in behavioural flexibility revealed by serial reversal of three-choice discrimination in rats

Contributions of different limbic cortical areas to mediation of behavioural flexibility were examined using repeated acquisition of three-choice discrimination in operant chambers. Rats were trained on a series of positional discrimination tasks with three levers, where position of the correct lever remained the same within a task but shifted across tasks. Ibotenic acid lesions of the medial prefrontal cortex impaired acquisition of each discrimination task by increasing errors specifically in the early phase of each task. These errors were characterised by perseveration to the previously correct lever. By contrast, lesions of the anterior cingulate cortex resulted in the impairment of discrimination in general without inducing perseveration; the impairment was instead characterised by disruption of general error-correction processes. Hippocampal lesions severely impaired learning by increasing perseverative tendencies that were present throughout the learning stages in each task. These results extend our understanding of the contributions of the different nodes of the limbic cortico-striatal circuit to different aspects of behavioural flexibility.

► We studied different aspects of behavioural flexibility in serial reversal in rats.
► mPFC lesions selectively increased perseveration early in each discrimination task.
► ACC lesions disrupted error-correction, leading to general discrimination failure.
► HPC lesions increased overall perseverative tendency.
► We demonstrated dissociable roles of these limbic cortices in flexible behaviour.