The brain can flexibly reorganize motor sequence, or program, execution to efficiently reach positive outcomes. These behavioral adaptations are primarily driven by reinforcement learning, leading to structural and kinematic modifications of consolidated motor programs. While previous studies established the critical contribution of cortical and basal ganglia circuits in controlling motor sequences or movement-by-movement kinematics, the neural mechanisms that adaptively shape efficient motor programs are not fully understood. Here, we found increased action-locked activity and network synchrony of somatostatin (SST) interneurons in the primary motor cortex (M1), compared to desynchronized pyramidal (PYR) neuron calcium activity, upon the acquisition of a single lever-press task in freely moving mice. After motor consolidation, cortical SST interneurons disengaged from action execution and then re-engaged when mice reorganized their motor programs upon changes in task complexity. Notably, the activity of M1 SST interneurons encoded structural and kinematic information of these more complex motor sequences. Finally, we showed that inhibition of SST interneurons interfered with the kinematics and disrupted the efficiency of motor program execution. These findings demonstrate a causal role for M1 SST interneuron re-engagement in regulating efficient motor sequence reorganization.

Highlights

• Activation of somatostatin (SST) interneurons in the primary motor cortex (M1) correlates with learning new motor actions and execution of complex motor programs.
• Activity of M1 SST interneurons adapts in response to structural patterns of the motor tasks.
• Inhibition of SST interneuron activity leads to inefficient execution of complex motor programs.