Since the remarkable discovery of adult neurogenesis in the mammalian hippocampus, considerable effort has been devoted to unraveling the functional significance of these new neurons. Our group has proposed that a continual turnover of neurons in the DG could contribute to the development of event-unique memory traces that act to reduce interference between highly similar inputs. To test this theory, we implemented a recognition task containing some objects that were repeated across trials as well as some objects that were highly similar, but not identical, to ones previously observed. The similar objects, termed lures, overlap substantially with previously viewed stimuli, and thus, may require hippocampal neurogenesis in order to avoid catastrophic interference. Lifestyle factors such as aerobic exercise and stress have been shown to impact the local neurogenic microenvironment, leading to enhanced and reduced levels of DG neurogenesis, respectively. Accordingly, we hypothesized that healthy young adults who take part in a long-term aerobic exercise regime would demonstrate enhanced performance on the visual pattern separation task, specifically at correctly categorizing lures as “similar.” Indeed, those who experienced a proportionally large change in fitness demonstrated a significantly greater improvement in their ability to correctly identify lure stimuli as “similar.” Conversely, we expected that those who score high on depression scales, an indicator of chronic stress, would exhibit selective deficits at appropriately categorizing lures. As expected, those who scored high on the Beck Depression Inventory (BDI) were significantly worse than those with relatively lower BDI scores at correctly identifying lures as “similar,” while performance on novel and repeated stimuli was identical. Taken together, our results support the hypothesis that adult-born neurons in the DG contribute to the orthogonalization of incoming information.

Adult hippocampal neurogenesis (AHN) is downregulated by numerous lifestyle factors including chronic stress. While the functional significance of AHN remains elusive, computational models and empirical evidence implicate immature neurons in minimizing interference between similar memories-a process termed pattern separation. The role of neurogenesis in remote memory is less clear. Some have proposed that neurogenesis promotes the clearance of old memories from the hippocampus, while others have proposed that neurogenesis promotes long-term retention of memories within the hippocampus. We used a modified version of the behavioral pattern separation task originally described by Kirwan and Stark (2007). In this task, some objects are repeated across trials, some are similar lures and the rest are novel. Participants are asked to classify each object as old, new, or similar. The correct classification of lures as similar may tax pattern separation processes in the hippocampus and AHN. To investigate the potential role of AHN in remote memory, we introduced a 2-week delay between the presentation and recognition of certain stimuli. As in previous studies, we found that those with higher depression scores made significantly more errors at identifying lures as similar when presentation and recognition were separated by a brief delay. When presentation and recognition trials were separated by a longer delay, the correct classification of lures dropped to chance levels for all groups, but now lower stress and depression scores were associated with superior identification of exact repetitions. Our data suggest a role for AHN in the stabilization of remote memories.

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