Adult-born neurons promote cognitive flexibility by improving memory precision and indexing.

Adult neurogenesis in the hippocampal dentate gyrus (DG) is an extraordinary form of plasticity fundamental for cognitive flexibility. Recent evidence showed that newborn neurons differentially modulate input to the infra- and supra-pyramidal blades of the DG during the processing of spatial and contextual information, respectively. However, how this differential regulation by neurogenesis is translated into different aspects contributing cognitive flexibility is unclear. Here, we increased adult-born neurons by a genetic expansion of neural stem cells and studied their influence during navigational learning. We found that increased neurogenesis improved both memory precision and flexibility. Interestingly, each of these gains was associated with distinct subregional patterns of activity and better separation of memory representations in the DG-CA3 network. Our results highlight the role of adult-born neurons in promoting memory precision and indexing and suggests their anatomical allocation within specific DG-CA3 compartments, together contributing to cognitive flexibility.