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Closed-loop brain stimulation augments fear extinction in male rats

Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although...

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Autores principales: Sierra, Rodrigo Ordoñez, Pedraza, Lizeth Katherine, Barcsai, Lívia, Pejin, Andrea, Li, Qun, Kozák, Gábor, Takeuchi, Yuichi, Nagy, Anett J., Lőrincz, Magor L., Devinsky, Orrin, Buzsáki, György, Berényi, Antal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322911/
https://www.ncbi.nlm.nih.gov/pubmed/37407557
http://dx.doi.org/10.1038/s41467-023-39546-7
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author Sierra, Rodrigo Ordoñez
Pedraza, Lizeth Katherine
Barcsai, Lívia
Pejin, Andrea
Li, Qun
Kozák, Gábor
Takeuchi, Yuichi
Nagy, Anett J.
Lőrincz, Magor L.
Devinsky, Orrin
Buzsáki, György
Berényi, Antal
author_facet Sierra, Rodrigo Ordoñez
Pedraza, Lizeth Katherine
Barcsai, Lívia
Pejin, Andrea
Li, Qun
Kozák, Gábor
Takeuchi, Yuichi
Nagy, Anett J.
Lőrincz, Magor L.
Devinsky, Orrin
Buzsáki, György
Berényi, Antal
author_sort Sierra, Rodrigo Ordoñez
collection PubMed
description Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation of the medial forebrain bundle (MFB) can enhance fear extinction consolidation in male rats. The modified fear memories became resistant to induced recall (i.e., ‘renewal’ and ‘reinstatement’) and did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. Our results demonstrate that SWR-triggered closed-loop stimulation of the MFB reward system enhances extinction of fearful memories and reducing fear expression across different contexts and preventing excessive and persistent fear responses. These findings highlight the potential of neuromodulation to augment extinction learning and provide a new avenue to develop treatments for anxiety disorders.
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spelling pubmed-103229112023-07-07 Closed-loop brain stimulation augments fear extinction in male rats Sierra, Rodrigo Ordoñez Pedraza, Lizeth Katherine Barcsai, Lívia Pejin, Andrea Li, Qun Kozák, Gábor Takeuchi, Yuichi Nagy, Anett J. Lőrincz, Magor L. Devinsky, Orrin Buzsáki, György Berényi, Antal Nat Commun Article Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation of the medial forebrain bundle (MFB) can enhance fear extinction consolidation in male rats. The modified fear memories became resistant to induced recall (i.e., ‘renewal’ and ‘reinstatement’) and did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. Our results demonstrate that SWR-triggered closed-loop stimulation of the MFB reward system enhances extinction of fearful memories and reducing fear expression across different contexts and preventing excessive and persistent fear responses. These findings highlight the potential of neuromodulation to augment extinction learning and provide a new avenue to develop treatments for anxiety disorders. Nature Publishing Group UK 2023-07-05 /pmc/articles/PMC10322911/ /pubmed/37407557 http://dx.doi.org/10.1038/s41467-023-39546-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sierra, Rodrigo Ordoñez
Pedraza, Lizeth Katherine
Barcsai, Lívia
Pejin, Andrea
Li, Qun
Kozák, Gábor
Takeuchi, Yuichi
Nagy, Anett J.
Lőrincz, Magor L.
Devinsky, Orrin
Buzsáki, György
Berényi, Antal
Closed-loop brain stimulation augments fear extinction in male rats
title Closed-loop brain stimulation augments fear extinction in male rats
title_full Closed-loop brain stimulation augments fear extinction in male rats
title_fullStr Closed-loop brain stimulation augments fear extinction in male rats
title_full_unstemmed Closed-loop brain stimulation augments fear extinction in male rats
title_short Closed-loop brain stimulation augments fear extinction in male rats
title_sort closed-loop brain stimulation augments fear extinction in male rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322911/
https://www.ncbi.nlm.nih.gov/pubmed/37407557
http://dx.doi.org/10.1038/s41467-023-39546-7
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