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The primary motor cortex (M1) is known to be a critical site for movement initiation and motor learning. Surprisingly, it has also been shown to possess reward-related activity, presumably to facilitate reward-based learning of new movements. However, it is unclear whether and how reward-related signals are represented among different cell types in M1 during learning, and which brain regions might confer this information to M1. Using in vivo two-photon calcium imaging in head-fixed mice during an associative learning task, we found that both VIP+ and PV+ inhibitory neurons were responsive to reward and reward-related cues. After learning, VIP+ cells became preferentially more responsive to reward while PV+ cells became more responsive to reward-related cues. In addition, we utilized a monosynaptic rabies tracing strategy to generate a brain-wide map of long-range input to VIP, PV, and SST inhibitory neurons as well as pyramidal neurons, to identify brain regions that might confer reward-related activity to VIP+ cells in M1. Together, this work uncovers neural circuits involved in modulating M1 activity in response to reward.
