Activity-Dependent Remodeling of Corticostriatal Axonal Boutons During Motor Learning

Motor skill learning induces long-lasting synaptic plasticity at not only the inputs, such as dendritic spines^1-4, but also at the outputs to the striatum of motor cortical neurons^5,6. However, very little is known about the activity and structural plasticity of corticostriatal axons during learning in the adult brain. Here, we used longitudinal in vivo two-photon imaging to monitor the activity and structure of thousands of corticostriatal axonal boutons in the dorsolateral striatum in awake mice. We found that learning a new motor skill induces dynamic regulation of axonal boutons. The activities of motor corticostriatal axonal boutons exhibited selectivity for rewarded movements (RM) and un-rewarded movements (UM). Strikingly, boutons on the same axonal branches showed diverse responses during behavior. Motor learning significantly increased the fraction of RM boutons and reduced the heterogeneity of bouton activities. Moreover, motor learning-induced profound structural dynamism in boutons. By combining structural and functional imaging, we identified that newly formed axonal boutons are more likely to exhibit selectivity for RM and are stabilized during motor learning, while UM boutons are selectively eliminated. Our results highlight a novel form of plasticity at corticostriatal axons induced by motor learning, indicating that motor corticostriatal axonal boutons undergo dynamic reorganization that facilitates the acquisition and execution of motor skills.