Decreased Dorsomedial Striatum Direct Pathway Neuronal Activity Is Required for Learned Motor Coordination

It has been suggested that the dorsomedial striatum (DMS) is engaged in the early stages of motor learning for goal-directed actions, whereas at later stages, control is transferred to the dorsolateral striatum (DLS), a process that enables learned motor actions to become a skill or habit. It is not known whether these striatal regions are simultaneously active while the expertise is acquired. To address this question, we developed a mouse Treadmill Training Task that tracks changes in mouse locomotor coordination during running practice and simultaneously provides a means to measure local neuronal activity using photometry. To measure change in motor coordination over treadmill practice sessions, we used DeepLabCut (DLC) and custom-built code to analyze body position and paw movements. By evaluating improvements in motor coordination during training with simultaneous neuronal calcium activity in the striatum, we found that DMS direct pathway neurons exhibited decreased activity as the mouse gained proficiency at running. In contrast, direct pathway activity in the DLS was similar throughout training. Pharmacological blockade of D1 dopamine receptors in these subregions during task performance demonstrated that dopamine neurotransmission in the direct pathway activity is necessary for efficient motor coordination learning. These results provide new tools to measure changes in fine motor skills with simultaneous recordings of brain activity and reveal fundamental features of the neuronal substrates of motor learning.

Automated summary

This study investigates the roles of the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) in motor learning using a mouse Treadmill Training Task and photometry. The results show that as mice become more proficient at running, activity in the DMS direct pathway decreases, while direct pathway activity in the DLS remains similar throughout training. Additionally, the study demonstrates the importance of dopamine neurotransmission in efficient motor coordination learning.