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Significance The striatum is a brain region critical for motor and procedure learning. The distinct roles of the two neural pathways through the striatum, known as the direct and indirect pathways, remain to be clarified. Using two-photon calcium imaging of neuronal activity of the same population of dorsolateral striatum (DLS) neurons in behaving mice throughout the learning of a cue-triggered motor task, we discovered that DLS neuronal populations in these two pathways developed stable sequential firing patterns of a distinct time course after motor learning, with direct pathway neurons involved in the initiation of the learned motor action and indirect pathways responsible for suppressing erroneous motor actions. Thus, both pathways are required for motor learning and proper execution of learned motor behaviors.

Emergence of stable striatal D1R and D2R neuronal ensembles with distinct firing sequence during motor learning