Striatal cholinergic interneurons exert inhibition on competing default behaviours controlled by the nucleus...

With repeated practice, learned actions become more skilled, and eventually highly stereotypical. This transition is accompanied by a shift in striatal control over behaviour from ventral and dorsomedial striatum to dorsolateral striatum. The cholinergic interneurons (CINs) in the striatum are central to striatal computation. Yet, their role in the transition from motivated to stereotypic behaviour is still unclear. In this study, we examined whether CINs contribute to the competition between both control systems. We selectively lesioned CINs in the nucleus accumbens (NAc) or in the dorsolateral striatum (DLS) of rats trained in a cued maze task. After obtaining skilled performance, we manipulated the motivation for reward. While sparing task acquisition, selective lesions of the CINs had a marked dissociable impact on the sensitivity to motivation in the highly skilled state. Selective lesions of CINs increased automaticity of behaviour when performed in the DLS, but increased sensitivity to motivation in the NAc. These findings indicate a central role of CINs in regulating motivational impact on striatally controlled behaviours.