Environmental enrichment accelerates the stabilization of cortical representation during de novo learning.

Environmental enrichment is an established strategy to enhance learning and to build resilience against neurodegeneration. This work aimed to study the functional encoding dynamics of cortical neurons in enriched mice performing a virtual spatial foraging task. Thy1-GCaMP6s mice were enriched by running a complex obstacle course, with different types of hurdles requiring climbing, jumping, and/or balancing elements. Two-photon calcium imaging was conducted on populations of neurons from the secondary motor cortex before, during, and after repeated locomotion through a virtual environment with visual-tactile cues. We observed an increase in memory reactivation during the first day of exposure. With training, enriched animals exhibited a stronger anticipatory response near the reward location. Moreover, cortical neurons became substantially more stable over days. Altogether, these results indicate that prior environmental enrichment accelerates the stabilization of cortical activity during learning and enables faster and more robust acquisition of new sequence representations of a novel task.