Fast pathway-specific reorganization of barrel cortex underlying rapid goal-directed sensorimotor learning

Animals exhibit flexible and adaptive behavior in novel situations, in part relying on reward-based learning. Although the reinforcement of positive outcomes plays a central role in shaping behavior, the neural circuit mechanisms of goal-directed sensorimotor transformation remain incompletely understood. Common behavioral paradigms for studying such mechanisms are hindered by the prolonged training period needed to reach expert performance, impeding the real-time observation of plastic changes. Here, we developed a rapid whisker-based detection task where thirsty mice learn to associate a novel stimulus with licking of a water reward spout in the course of a few minutes within a single behavioral session. Inactivation experiments via pharmacology and optogenetics demonstrated the necessity of barrel cortex activity in this learning process. Performing longitudinal two-photon calcium imaging of barrel cortex before, during and after the learning session revealed network reorganization with a long-lasting increase in the whisker-evoked responses of a subpopulation of L2/3 excitatory neurons after learning. To assess how these changes might contribute to reward-based learning by routing sensory information differentially to distinct downstream cortical regions responsible for task execution, we further investigated the involvement of L2/3 barrel cortex neurons projecting to the secondary somatosensory (S2p) and the primary motor (M1p) cortices. Consistent with previous work, S2p neurons exhibited a significant increase in activity after learning, while M1p neurons remained unchanged. Taken together, these results indicate that our rapid-learning task constitutes a promising paradigm to uncover the plasticity rules and synaptic mechanisms governing reward-based learning.