Rule encoding in dorsal striatum impacts action selection.

Cognitive flexibility is a hallmark of prefrontal cortical (PFC) function yet little is known about downstream area involvement. The medial dorsal striatum (mDS) receives major projections from the PFC and is uniquely situated to perform the integration of responses with rule information. In this study, we use a novel rule shifting task in rats that mirrors non-human primate and human studies in its temporal precision and counterbalanced responses. We record activity from single neurons in the mDS while rats switch between different rules for reward. Additionally, we pharmacologically inactivate mDS by infusion of a baclofen/muscimol cocktail. Inactivation of mDS impaired the ability to shift to a new rule and increased the number of regressive errors. While recording in mDS, we identified neurons modulated by direction whose activity reflected the conflict between competing rule information. We show that a subset of these neurons was also rule selective, and that the conflict between competing rule cues was resolved as behavioural performance improved. Other neurons were modulated by rule, but not direction. These neurons became selective before behavioural performance accurately reflected the current rule. These data provide an additional locus for investigating the mechanisms underlying behavioural flexibility. Converging lines of evidence from multiple human psychiatric disorders have implicated dorsal striatum as an important and understudied neural substrate of flexible cognition. Our data confirm the importance of mDS, and suggest a mechanism by which mDS mediates abstract cognition functions.