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Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus
Early life experiences program lifelong responses to stress. In agreement, resilience and vulnerability to psychopathologies, such as posttraumatic stress disorder (PTSD), have been suggested to depend on the early background. New therapies have targeted memory reconsolidation as a strategy to modif...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546926/ https://www.ncbi.nlm.nih.gov/pubmed/31191245 http://dx.doi.org/10.3389/fnmol.2019.00134 |
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author | Couto-Pereira, Natividade de Sá Lampert, Carine Vieira, Aline dos Santos Lazzaretti, Camilla Kincheski, Grasielle Clotildes Espejo, Pablo Javier Molina, Victor Alejandro Quillfeldt, Jorge Alberto Dalmaz, Carla |
author_facet | Couto-Pereira, Natividade de Sá Lampert, Carine Vieira, Aline dos Santos Lazzaretti, Camilla Kincheski, Grasielle Clotildes Espejo, Pablo Javier Molina, Victor Alejandro Quillfeldt, Jorge Alberto Dalmaz, Carla |
author_sort | Couto-Pereira, Natividade de Sá |
collection | PubMed |
description | Early life experiences program lifelong responses to stress. In agreement, resilience and vulnerability to psychopathologies, such as posttraumatic stress disorder (PTSD), have been suggested to depend on the early background. New therapies have targeted memory reconsolidation as a strategy to modify the emotional valence of traumatic memories. Here, we used animal models to study the molecular mechanism through which early experiences may later affect aversive memory reconsolidation. Handling (H)—separation of pups from dams for 10 min—or maternal separation (MS) — 3-h separation—were performed from PDN1–10, using non-handled (NH) litters as controls. Adult males were trained in a contextual fear conditioning (CFC) task; 24 h later, a short reactivation session was conducted in the conditioned or in a novel context, followed by administration of midazolam 3 mg/kg i.p. (mdz), known to disturb reconsolidation, or vehicle; a test session was performed 24 h after. The immunocontent of relevant proteins was studied 15 and 60 min after memory reactivation in the dorsal hippocampus (dHc) and basolateral amygdala complex (BLA). Mdz-treated controls (NH) showed decreased freezing to the conditioned context, consistent with reconsolidation impairment, but H and MS were resistant to labilization. Additionally, MS males showed increased freezing to the novel context, suggesting fear generalization; H rats showed lower freezing than the other groups, in accordance with previous suggestions of reduced emotionality facing adversities. Increased levels of Zif268, GluN2B, β-actin and polyubiquitination found in the BLA of all groups suggest that memory reconsolidation was triggered. In the dHc, only NH showed increased Zif268 levels after memory retrieval; also, a delay in ERK1/2 activation was found in H and MS animals. We showed here that reconsolidation of a contextual fear memory is insensitive to interference by a GABAergic drug in adult male rats exposed to different neonatal experiences; surprisingly, we found no differences in the reconsolidation process in the BLA, but the dHc appears to suffer temporal desynchronization in the engagement of reconsolidation. Our results support a hippocampal-dependent mechanism for reconsolidation resistance in models of early experiences, which aligns with current hypotheses for the etiology of PTSD. |
format | Online Article Text |
id | pubmed-6546926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65469262019-06-12 Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus Couto-Pereira, Natividade de Sá Lampert, Carine Vieira, Aline dos Santos Lazzaretti, Camilla Kincheski, Grasielle Clotildes Espejo, Pablo Javier Molina, Victor Alejandro Quillfeldt, Jorge Alberto Dalmaz, Carla Front Mol Neurosci Neuroscience Early life experiences program lifelong responses to stress. In agreement, resilience and vulnerability to psychopathologies, such as posttraumatic stress disorder (PTSD), have been suggested to depend on the early background. New therapies have targeted memory reconsolidation as a strategy to modify the emotional valence of traumatic memories. Here, we used animal models to study the molecular mechanism through which early experiences may later affect aversive memory reconsolidation. Handling (H)—separation of pups from dams for 10 min—or maternal separation (MS) — 3-h separation—were performed from PDN1–10, using non-handled (NH) litters as controls. Adult males were trained in a contextual fear conditioning (CFC) task; 24 h later, a short reactivation session was conducted in the conditioned or in a novel context, followed by administration of midazolam 3 mg/kg i.p. (mdz), known to disturb reconsolidation, or vehicle; a test session was performed 24 h after. The immunocontent of relevant proteins was studied 15 and 60 min after memory reactivation in the dorsal hippocampus (dHc) and basolateral amygdala complex (BLA). Mdz-treated controls (NH) showed decreased freezing to the conditioned context, consistent with reconsolidation impairment, but H and MS were resistant to labilization. Additionally, MS males showed increased freezing to the novel context, suggesting fear generalization; H rats showed lower freezing than the other groups, in accordance with previous suggestions of reduced emotionality facing adversities. Increased levels of Zif268, GluN2B, β-actin and polyubiquitination found in the BLA of all groups suggest that memory reconsolidation was triggered. In the dHc, only NH showed increased Zif268 levels after memory retrieval; also, a delay in ERK1/2 activation was found in H and MS animals. We showed here that reconsolidation of a contextual fear memory is insensitive to interference by a GABAergic drug in adult male rats exposed to different neonatal experiences; surprisingly, we found no differences in the reconsolidation process in the BLA, but the dHc appears to suffer temporal desynchronization in the engagement of reconsolidation. Our results support a hippocampal-dependent mechanism for reconsolidation resistance in models of early experiences, which aligns with current hypotheses for the etiology of PTSD. Frontiers Media S.A. 2019-05-28 /pmc/articles/PMC6546926/ /pubmed/31191245 http://dx.doi.org/10.3389/fnmol.2019.00134 Text en Copyright © 2019 Couto-Pereira, Lampert, Vieira, Lazzaretti, Kincheski, Espejo, Molina, Quillfeldt and Dalmaz. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Couto-Pereira, Natividade de Sá Lampert, Carine Vieira, Aline dos Santos Lazzaretti, Camilla Kincheski, Grasielle Clotildes Espejo, Pablo Javier Molina, Victor Alejandro Quillfeldt, Jorge Alberto Dalmaz, Carla Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus |
title | Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus |
title_full | Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus |
title_fullStr | Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus |
title_full_unstemmed | Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus |
title_short | Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus |
title_sort | resilience and vulnerability to trauma: early life interventions modulate aversive memory reconsolidation in the dorsal hippocampus |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546926/ https://www.ncbi.nlm.nih.gov/pubmed/31191245 http://dx.doi.org/10.3389/fnmol.2019.00134 |
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