Gradual consolidation of skilled sequential movements in primary motor cortex of non-human primates

Many of our daily actions rely on skilled sequential movements. Sequence performance improves with practice and can reach expert levels with years of repeated practice, truly exemplifying the saying “Practice makes perfect”. Human and non-human primate studies have shown structural and functional changes in the primary motor cortex (M1) following extended practice of sequential movements, suggesting M1’s involvement in acquisition and retention of skilled sequences. However, it has been challenging to causally examine M1’s role in sequence learning, as inactivation or lesion of M1 impairs movement production. Here, we causally examined M1’s contribution to sequence learning by locally inhibiting protein synthesis in M1. Our results show that protein synthesis inhibition in M1 disrupted memory-guided sequential movements at all stages of learning without affecting movement production, though the effects decreased with continued practice. These findings suggest that neural traces for sequential movements are repeatedly consolidated in M1 through protein synthesis, with the rate of consolidation slowing as learning progresses.