Abstract
Adult neurogenesis in the dentate gyrus of the hippocampal formation has been implicated in several forms of hippocampus-dependent memory. However, its role in the persistence of remote memory is unknown. Furthermore, whether the hippocampus plays a role in maintaining remote contextual memories is controversial. Here we used an inducible gene-specific approach for conditional deletion of erk5 in the adult neurogenic regions of the mouse brain to specifically impair adult neurogenesis. The erk5 gene was conditionally deleted under three different experimental conditions: prior to training for contextual fear, 6 days after training, or 5 weeks after training, We present evidence that remote memory was impaired under all three conditions. These data demonstrate that ongoing adult neurogenesis is required both for the initial establishment and the continued maintenance of remote contextual fear memory, even after the remote memory has transferred into extra-hippocampal regions of the brain 5 weeks after training.
Highlights
Adult neurogenesis occurs in distinct regions in the mammalian brain under normal physiological conditions including the subgranular zone (SGZ) in the dentate gyrus of the hippocampal formation [1]
We previously reported that ERK5 expression in the adult brain is limited to the neurogenic regions and that adult neurogenesis in the SGZ is regulated by the ERK5 MAP kinase both in vitro and in vivo [3]
Our data suggest that the impaired contextual fear memory of ERK5 inducible and conditional ERK5 knockout (icKO) mice 6 d after training using the weak foot shock paradigm is not due to a deficit in acquisition or memory retrieval, but rather consolidation and persistence of contextual fear memory
Summary
Adult neurogenesis occurs in distinct regions in the mammalian brain under normal physiological conditions including the subgranular zone (SGZ) in the dentate gyrus of the hippocampal formation [1]. Adult neurogenesis in the SGZ has been implicated in several forms of hippocampus-dependent learning and memory [2]. Whether the maintenance of remote contextual memory depends on the hippocampal formation is controversial with some evidence supporting its involvement [5,6,7]. Adult neurogenesis occurs throughout adult life in the dentate gyrus and may modulate the duration of hippocampus-dependent memory [13], its role in the maintenance of remote memory has not been reported. We present evidence that remote contextual memory depends upon ongoing adult neurogenesis even after remote memory is established
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