Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval.
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.
Department of Biosciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Japan.
Rie
R
Ishikawa
Department of Biosciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Japan.|Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan.
Hotaka
H
Fukushima
Program in Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, Canada.
Paul W
http://orcid.org/0000-0002-1395-3586
PW
Frankland
Department of Biosciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Japan.|Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan.
Satoshi
http://orcid.org/0000-0002-8038-9583
S
Kida
hippocampus; mouse; neurogenesis; neuroscience; remote fear memory
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