Reinforcement sculpts synaptic ensembles for operant dendritic control

Reinforcement learning requires the selective modification of synapses that contribute to outcome-relevant neural activity, yet the principles underlying these selective modifications remain unclear. Here we combined longitudinal two-photon imaging of identified dendritic spines with a closed-loop optical brain-machine interface (BMI), in which activity from selected apical dendrites of layer 5 motor-cortical neurons controlled an auditory cursor, with target acquisition triggering optogenetic reinforcement. Mice learned to reliably generate the specific dendritic activity that leads to reinforcement. Learning was accompanied by selective strengthening and weakening of individual spines on reinforced dendrites. At individual synapses, the direction of plasticity depended on both the timing of activity relative to reinforced dendritic events and the pre-existing temporal organization of that activity. Furthermore, plasticity was enriched in small task-relevant synaptic groups: spines in synergistic groups were preferentially strengthened, whereas those in antagonistic groups were preferentially weakened. These changes were accompanied by the emergence of increasingly reproducible, selectively recruited, and temporally focused synaptic ensembles, and the incorporation of newly formed spines into these ensembles. Finally, blocking striatal dopamine receptor signaling impaired BMI learning and cortical synaptic reorganization of target dendrites, demonstrating a role for striatal reinforcement in cortical plasticity. Together, these findings reveal how reinforcement of specific dendritic activity sculpts synaptic ensembles that support learned operant dendritic control.