Opposing Roles of the Dorsolateral and Dorsomedial Striatum in the Acquisition of Skilled Action Sequencing in Rats

Abstract

The shift in control from dorsomedial to dorsolateral striatum during skill and habit formation has been well established, but whether striatal subregions orchestrate this shift cooperatively or competitively remains unclear. Cortical inputs have also been implicated in the shift toward automaticity, but it is unknown whether they mirror their downstream striatal targets across this transition. We addressed these questions using a five step heterogeneous action sequencing task in male rats that is optimally performed by automated chains of actions. By optimizing automatic habitual responding, we discovered that loss of function in the dorsomedial striatum accelerated sequence acquisition. In contrast, loss of function in the dorsolateral striatum impeded acquisition of sequencing, demonstrating functional opposition within the striatum. Unexpectedly, the mPFC was not involved; however, the lateral orbitofrontal cortex was critical. These results shift current theories about striatal control of behavior to a model of competitive opposition, where the dorsomedial striatum interferes with the development of dorsolateral-striatum dependent behavior.SIGNIFICANCE STATEMENTWe provide the most direct evidence to date that the dorsomedial and dorsolateral striatum compete for control in the acquisition of habitual action sequences. The dorsolateral striatum was critical for sequencing behavior, but loss of dorsomedial striatum function enhanced acquisition. In addition, we found that the mPFC was not required for the formation of automated actions. Using a task that optimizes habitual responding, we demonstrate that the arbitration of dorsomedial and dorsolateral control is not modulated by medial prefrontal cortical activity. However, we find evidence for the role of the lateral orbitofrontal cortex in action sequencing. These results have implications for our understanding of how habits and skills form.