The Natural Variability of a Dexterous Motor Skill Is Stably Encoded in the Cortex of Freely Behaving Mice

The nervous system enables precise, skilled movements across diverse contexts, consistently performed day after day. However, the extent to which the brain's neural activity patterns are specific to each instance of a movement or behavior, and how similar these patterns are across days, remains unclear. To address this, we record calcium fluorescence activity in the motor cortex of freely moving mice performing a self-initiated, skilled reach-to-grasp task. The high trial counts and single-trial variability in this task allow for a rigorous statistical analysis of moment-to-moment movement encoding across matched behavioral sets over five days. We found that single neurons in motor cortex encode the single trial (reach-to-reach) details of paw, digit, and head movements, and this encoding is stable over days. This suggests that the stable contribution of individual cells in the motor circuit underlies the generation of skilled movements, even in complex sensory-driven tasks like reach-to-grasp.