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Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval
Memory retrieval of fearful experiences is essential for survival but can be maladaptive if not appropriately suppressed. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic subregion Nucleus Reuniens (NR) is necessary for contextual...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081195/ https://www.ncbi.nlm.nih.gov/pubmed/37034812 http://dx.doi.org/10.1101/2023.03.27.534420 |
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author | Ratigan, Heather C. Krishnan, Seetha Smith, Shai Sheffield, Mark E. J. |
author_facet | Ratigan, Heather C. Krishnan, Seetha Smith, Shai Sheffield, Mark E. J. |
author_sort | Ratigan, Heather C. |
collection | PubMed |
description | Memory retrieval of fearful experiences is essential for survival but can be maladaptive if not appropriately suppressed. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic subregion Nucleus Reuniens (NR) is necessary for contextual fear extinction and strongly projects to hippocampal subregion CA1. However, the NR-CA1 pathway has not been investigated during behavior, leaving unknown its role in contextual fear memory retrieval. We implement a novel head-restrained virtual reality CFC paradigm and show that inactivation of the NR-CA1 pathway prolongs fearful freezing epochs, induces fear generalization, and delays extinction. We use in vivo sub-cellular imaging to specifically record NR-axons innervating CA1 before and after CFC. We find NR-axons become selectively tuned to freezing only after CFC, and this activity is well-predicted by an encoding model. We conclude that the NR-CA1 pathway actively suppresses fear responses by disrupting ongoing hippocampal-dependent contextual fear memory retrieval. |
format | Online Article Text |
id | pubmed-10081195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-100811952023-04-08 Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval Ratigan, Heather C. Krishnan, Seetha Smith, Shai Sheffield, Mark E. J. bioRxiv Article Memory retrieval of fearful experiences is essential for survival but can be maladaptive if not appropriately suppressed. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic subregion Nucleus Reuniens (NR) is necessary for contextual fear extinction and strongly projects to hippocampal subregion CA1. However, the NR-CA1 pathway has not been investigated during behavior, leaving unknown its role in contextual fear memory retrieval. We implement a novel head-restrained virtual reality CFC paradigm and show that inactivation of the NR-CA1 pathway prolongs fearful freezing epochs, induces fear generalization, and delays extinction. We use in vivo sub-cellular imaging to specifically record NR-axons innervating CA1 before and after CFC. We find NR-axons become selectively tuned to freezing only after CFC, and this activity is well-predicted by an encoding model. We conclude that the NR-CA1 pathway actively suppresses fear responses by disrupting ongoing hippocampal-dependent contextual fear memory retrieval. Cold Spring Harbor Laboratory 2023-03-27 /pmc/articles/PMC10081195/ /pubmed/37034812 http://dx.doi.org/10.1101/2023.03.27.534420 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Ratigan, Heather C. Krishnan, Seetha Smith, Shai Sheffield, Mark E. J. Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval |
title | Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval |
title_full | Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval |
title_fullStr | Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval |
title_full_unstemmed | Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval |
title_short | Direct Thalamic Inputs to Hippocampal CA1 Transmit a Signal That Suppresses Ongoing Contextual Fear Memory Retrieval |
title_sort | direct thalamic inputs to hippocampal ca1 transmit a signal that suppresses ongoing contextual fear memory retrieval |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081195/ https://www.ncbi.nlm.nih.gov/pubmed/37034812 http://dx.doi.org/10.1101/2023.03.27.534420 |
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