Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion

Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion. [Display omitted] ► Adult-born young granule cells in the dentate are required for pattern separation ► Older granule cells in the dentate are not required for pattern separation ► Older granule cells in the dentate contribute to rapid pattern completion ► As they age, adult granule cells switch from pattern separation to pattern completion Granule cells in the dentate gyrus of the hippocampus mediate two distinct forms of memory: pattern separation, the ability to distinguish between similar events, and pattern completion, the ability to recall a single event. Surprisingly, as these adult-born neurons age, they undergo a functional switch from initially participating solely in pattern separation to later only contributing to pattern completion.