Decreased dorsomedial striatum direct pathway neuronal activity is required for learned motor coordination.

Abstract

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 if 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 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.Significance statementMotor disorders, including Parkinson's Disease, present with several motor dysfunction, including degradation of motor learning. While individuals with PD are able to learn, certain aspects of learning, especially automatic responses to feedback, are damaged. Our current knowledge of motor learning comes from studies on models of motor dysfunction or analysis of simple in-laboratory skills that may not apply to more complex skills.In this work we developed the "treadmill training task" to track changes in mouse locomotor coordination during practice at running that simultaneously provides a means to measure local neuronal activity using photometry. This work will assist in the development of more efficient therapies for motor impairments due to a multitude of condition, including Parkinson's disease.