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Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear

Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coo...

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Autores principales: Totty, Michael S., Tuna, Tuğçe, Ramanathan, Karthik R., Jin, Jingji, Peters, Shaun E., Maren, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582091/
https://www.ncbi.nlm.nih.gov/pubmed/37848425
http://dx.doi.org/10.1038/s41467-023-42315-1
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author Totty, Michael S.
Tuna, Tuğçe
Ramanathan, Karthik R.
Jin, Jingji
Peters, Shaun E.
Maren, Stephen
author_facet Totty, Michael S.
Tuna, Tuğçe
Ramanathan, Karthik R.
Jin, Jingji
Peters, Shaun E.
Maren, Stephen
author_sort Totty, Michael S.
collection PubMed
description Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6–9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction.
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spelling pubmed-105820912023-10-19 Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear Totty, Michael S. Tuna, Tuğçe Ramanathan, Karthik R. Jin, Jingji Peters, Shaun E. Maren, Stephen Nat Commun Article Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6–9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction. Nature Publishing Group UK 2023-10-17 /pmc/articles/PMC10582091/ /pubmed/37848425 http://dx.doi.org/10.1038/s41467-023-42315-1 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Totty, Michael S.
Tuna, Tuğçe
Ramanathan, Karthik R.
Jin, Jingji
Peters, Shaun E.
Maren, Stephen
Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
title Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
title_full Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
title_fullStr Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
title_full_unstemmed Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
title_short Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
title_sort thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582091/
https://www.ncbi.nlm.nih.gov/pubmed/37848425
http://dx.doi.org/10.1038/s41467-023-42315-1
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