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

View Article: PubMed Central - PubMed

ABSTRACT

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

No MeSH data available.


The cannula tip placement in the hippocampus.(A–C) The cannula tip placement form mice infused with each drug as illustrated in Figure 4A (A), Figure 4B (B), and Figure 4C (C). Schematic drawings of coronal sections from all micro-infused animals (hippocampus, 1.94 mm posterior to the bregma). Only mice with needle tips within the boundaries of the hippocampus were included in the data analyses. ANI = anisomycin; VEH = vehicle.DOI:http://dx.doi.org/10.7554/eLife.17464.010
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fig4s1: The cannula tip placement in the hippocampus.(A–C) The cannula tip placement form mice infused with each drug as illustrated in Figure 4A (A), Figure 4B (B), and Figure 4C (C). Schematic drawings of coronal sections from all micro-infused animals (hippocampus, 1.94 mm posterior to the bregma). Only mice with needle tips within the boundaries of the hippocampus were included in the data analyses. ANI = anisomycin; VEH = vehicle.DOI:http://dx.doi.org/10.7554/eLife.17464.010

Mentions: Surgery was performed as described previously (Frankland et al., 2006; Suzuki et al., 2008; Mamiya et al., 2009; Kim et al., 2011; Suzuki et al., 2011; Zhang et al., 2011; Nomoto et al., 2012; Fukushima et al., 2014; Inaba et al., 2015). Under Nembutal anesthesia, and using standard stereotaxic procedures, a stainless steel guide cannula (22 gauge) was implanted into the dorsal hippocampus (−1.8 mm, ± 1.8 mm, −1.9 mm). Stereotaxic coordinates for dorsal hippocampus placement were based on the brain atlas of Franklin and Paxinos (1997). The mice were allowed to recover for at least one week after surgery. After that, they were handled for one week before the commencement of inhibitory avoidance. Only mice with a cannulation tip within the boundaries of the dorsal hippocampus were included in the data analyses. Cannulation tip placements are shown in Figure 4—figure supplement 1 and Figure 5—figure supplement 1.


Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval
The cannula tip placement in the hippocampus.(A–C) The cannula tip placement form mice infused with each drug as illustrated in Figure 4A (A), Figure 4B (B), and Figure 4C (C). Schematic drawings of coronal sections from all micro-infused animals (hippocampus, 1.94 mm posterior to the bregma). Only mice with needle tips within the boundaries of the hippocampus were included in the data analyses. ANI = anisomycin; VEH = vehicle.DOI:http://dx.doi.org/10.7554/eLife.17464.010
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036964&req=5

fig4s1: The cannula tip placement in the hippocampus.(A–C) The cannula tip placement form mice infused with each drug as illustrated in Figure 4A (A), Figure 4B (B), and Figure 4C (C). Schematic drawings of coronal sections from all micro-infused animals (hippocampus, 1.94 mm posterior to the bregma). Only mice with needle tips within the boundaries of the hippocampus were included in the data analyses. ANI = anisomycin; VEH = vehicle.DOI:http://dx.doi.org/10.7554/eLife.17464.010
Mentions: Surgery was performed as described previously (Frankland et al., 2006; Suzuki et al., 2008; Mamiya et al., 2009; Kim et al., 2011; Suzuki et al., 2011; Zhang et al., 2011; Nomoto et al., 2012; Fukushima et al., 2014; Inaba et al., 2015). Under Nembutal anesthesia, and using standard stereotaxic procedures, a stainless steel guide cannula (22 gauge) was implanted into the dorsal hippocampus (−1.8 mm, ± 1.8 mm, −1.9 mm). Stereotaxic coordinates for dorsal hippocampus placement were based on the brain atlas of Franklin and Paxinos (1997). The mice were allowed to recover for at least one week after surgery. After that, they were handled for one week before the commencement of inhibitory avoidance. Only mice with a cannulation tip within the boundaries of the dorsal hippocampus were included in the data analyses. Cannulation tip placements are shown in Figure 4—figure supplement 1 and Figure 5—figure supplement 1.

View Article: PubMed Central - PubMed

ABSTRACT

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

No MeSH data available.