Develop a task that can dissociate motor sequence learning and performance while remaining tractable for recording and perturbation studies in mice.

Pathological disruption of circuitry in the basal ganglia (BG) can result in an impaired ability to acquire and perform motor sequences. Animal models of Parkinson’s disease allow for highly specific and reproducible perturbation of BG function; however, there are few tasks for mice in which motor sequences have the precision and flexibility characteristic of human performance. Current tasks often confound aspects of performance (precise control over kinematics) with learning (knowledge of the sequence).

Our behavioral apparatus consists of interchangeable, touch-sensitive rungs which can be removed to create a unique sequence of gaps that mice cross to receive a reward. The slope of the apparatus can be altered, changing the kinematic requirements of the task independent of the sequence. Individual reach trajectories are reconstructed in 3D using stereo imaging, full sequence performance is recorded, and population activity in the striatum is collected using fiber photometry. Mice are assessed on both motor sequence learning and retention.

Pilot trials demonstrate mice learn individual sequences in relatively few trials and exhibit classic indicators of motor skill learning including reduced variability, increased speed, and fewer errors. With our task, motor deficits in models of Parkinson’s disease can be assessed with high resolution, and it can be determined whether these deficits are due to dysregulation of kinematics or the inability to learn a sequence.

The novel motor sequencing task described here allows us to study motor sequence learning in mice while independently tracking changes in performance (precise control over kinematics) and learning (knowledge of a sequence).