Division of progenitor cells in the subgranular zone leads to the continuous addition of new neurons to the adult hippocampus, a brain region that plays a central role in memory formation. Previously we used immunohistochemical approaches to visualize the recruitment of these adult-generated neurons into circuits supporting water maze and contextual fear memories in intact animals. We showed that integration proceeds in a maturationdependent manner, with new neurons not integrated in significant numbers until they are 4 weeks or older in age (Kee et al. 2007, Stone et al. 2010). Our new experiments address whether, once integrated, these neurons represent an essential component of a hippocampal memory trace. To address this question we developed a diphtheria toxin-based transgenic strategy which allowed us to tag adult-generated neurons and allow them to mature, and then ablate them either immediately before or after memory formation. Removal of this population of mature, adult-generated neurons had no effect on ongoing proliferation, but produced retrograde memory deficits in three different hippocampus-dependent tasks. As similar ablation one month after training produced equivalent retrograde amnesia, these results indicate that adultgenerated neurons form an essential and enduring component of hippocampal memory traces.
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