Cortex-wide laminar dynamics diverge during learning

Learning to link sensory information to motor actions involves dynamic coordination across cortical layers and regions. However, the involvement of a particular layer in learning, especially from a cortex-wide perspective, is relatively unknown. Using wide-field calcium imaging in mice as they learn a whisker-based go/no-go task, we tracked activity in layers 2/3 or 5 (L2/3 or L5) across 25 cortical areas. A surprising initial effect of learning was that activity in L5 but not in L2/3 was globally suppressed at auditory cue onset. As the texture comes into touch, we found that L2/3 displayed learning-related enhancements in higher order association areas rostrolateral (RL) and secondary somatosensory (S2), whereas L5 in these areas oppositely decreased. During texture touch, the barrel cortex (BC) displayed similar learning-related enhancement in both layers. As sensory information is transformed into a motor action, there was a frontal/posterior divergence that emerges after learning, in which L5 was enhanced in the frontal cortex and L2/3 was suppressed in the posterior cortex. In general, learning related correlations were often stronger between distant cortical layers than within the same column, suggesting that learning drives laminar interactions that transcend traditional columnar organization. Together, these results reveal that learning orchestrates a dynamic interplay of activity across space, time and cortical layers. Our findings emphasize the critical role of laminar architecture in shaping cortical plasticity and support the view that layer-specific circuits are fundamental to sensorimotor learning.