Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

R Ishikawa, H Fukushima, PW Frankland, S Kida - Elife, 2016 - elifesciences.org
R Ishikawa, H Fukushima, PW Frankland, S Kida
Elife, 2016elifesciences.org
Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which
increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress
disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of
recent, but not remote, memories. Here we show that, following prolonged re-exposure to
the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote
forgetting of remote contextual fear memory. However, these interventions are ineffective …
Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment.
DOI: http://dx.doi.org/10.7554/eLife.17464.001
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