Motor cortex somatostatin interneurons adaptively shape the structure of action sequences

The brain can flexibly reorganize the structure of action sequence, or motor programs, 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 the motor cortex is recognized as a crucial neural substrate for adaptive motor control and skill learning, the mechanisms by which cortical microcircuits actively fine-tune the timing and structure of action sequences, enabling organisms to adaptively maintain motor efficiency across varying task demands, remain unclear. Here, we found that the calcium activity of somatostatin (SST) interneurons (INs) in the primary motor cortex (M1) exhibits highly action-locked and synchronized calcium responses during the acquisition of a single lever-press task in freely moving mice. This neural representation contrasts with the sequential activation of pyramidal (PYR) neurons during the same task. After extended training with a consistent schedule and subsequent motor consolidation, M1 SST IN activity was no longer related to action execution. However, when the training schedule was progressively updated, leading mice to adapt their motor programs for more time-constrained, rapid action sequences, the action-related SST IN activity redistributed and did not decrease. Notably, this redistributed calcium activity of M1 SST INs correlated with structural modulation of ongoing action sequences. We identified two distinct neural activity patterns among non-overlapping SST IN populations: one encoding the initiation of action sequences and the other encoding trial-by-trial structural changes during the execution of complex action sequences. Moreover, inhibition of SST INs disrupted temporal structure of action sequences and decreased the efficiency of motor program execution. These findings highlight the unexpected role of M1 SST interneurons in actively refining motor programs into more efficient and task-specific structures. HIGHLIGHTSO_LIActivation of somatostatin (SST) interneurons in the primary motor cortex (M1) correlates with learning new motor actions and execution of complex motor programs. C_LIO_LIDistinct activity patterns of M1 SST interneurons actively encode the initiation and temporal structure of complex action sequences on a trial-by-trial basis C_LIO_LIInhibition of SST interneuron activity leads to inefficient execution of complex motor programs, with effects dependent on task specificity. C_LI