Unique potential of immature adult-born neurons for the remodeling of CA3 spatial maps

Mammalian hippocampal circuits undergo extensive remodeling through adult neurogenesis. While this process has been widely studied, the specific contribution of adult-born granule cells to spatial operations in the hippocampus remains unknown. Here, we show that optogenetic activation of 4-week-old (young) adult-born granule cells in free-foraging mice produces a non-reversible reconfiguration of spatial maps in proximal CA3 while rarely evoking neural activity. Stimulation of the same neuronal cohort on subsequent days recruits CA3 neurons with increased efficacy but fails to induce further remapping. In contrast, stimulation of 8-week-old (mature) adult-born granule cells can reliably activate CA3 cells but produces no alterations in spatial maps. Our results reveal a unique role of young adult-born granule cells in remodeling CA3 representations, a potential that can be depleted and is lost with maturation. This ability could contribute to generate orthogonalized downstream codes supporting pattern separation.