Abstract
The brain flexibly reorganizes action sequences to optimize behavioral outcomes through reinforcement learning and adaptive motor control. Although the primary motor cortex (M1) is essential for skill learning and dexterous movement, how cortical microcircuits refine the timing and structure of action sequences remains unclear. We show that M1 somatostatin interneurons (SST-Ins) display synchronized, action-locked calcium activity during acquisition of a lever-press task in freely moving mice, in contrast to the sequential activation of pyramidal neurons. Following extended training under a stable task schedule, SST-IN activity was no longer coupled to action execution. However, when task demands were modified to require faster and more temporally constrained action sequences, SST-IN activity redistributed and correlated with trial-by-trial changes in sequences, rather than diminishing. Inhibition of SST-INs disrupted temporal organization and impaired efficient motor execution. These findings highlight the unexpected role of M1 SST-INs in refining motor programs into more efficient and task-specific structures.
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Raw data can be found in Source Data file provided with this paper. Source data are provided with this paper.
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Examples of custom codes used in this manuscript are deposited in the database and publicly accessible at https://github.com/Jeongoenlee/SST.
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Acknowledgements
We would like to thank Drs. Karina Abrahao, Armando Salinas, Shana Augustin for advice on the project, technical support, and personal training. We also thank Drs. Joseph Cheer, Qing Liu, Kuan Hong Wang, Morgana Favero on technical support on head-mounted microscope systems, Dr. Andrew Kesner for help in use of the optogenetic laser controller, and Guoxiang Luo and Aurora Sheridan for tissue sample preparation. This work was supported by the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
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J.O.L., S.B., and D.M.L. conceived and designed the study. J.O.L. performed imaging, software programming, and behavior experiments, and all data analysis with input from S.B. and D.M.L. G.S. performed brain slice electrophysiology experiments with input from S.B. and D.M.L. A.H. performed behavioral experiments, input from J.O.L. and D.M.L. J.O.L., S.B., G.S., A.H., and D.M.L. discussed data and wrote the manuscript. D.M.L., J.O.L., and S.B. directed the project.
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Lee, J.O., Bariselli, S., Sitzia, G. et al. Motor cortex somatostatin interneurons adaptively shape the structure of action sequences. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70353-y
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DOI: https://doi.org/10.1038/s41467-026-70353-y
