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.Howard Hughes Medical InstituteOtsuka Maryland Research InstituteJeffry M. and Barbara Picower FoundationEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (NICHD intramural funding)National Institutes of Health (U.S.) (NIH grant R01-MH62122)National Institutes of Health (U.S.) (NIH grant R01-MH078821)National Institutes of Health (U.S.) (NIH grant P50-MH58880