A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination
Abstract The adaptive regulation of fear memories is a crucial neural function that prevents inappropriate fear expression. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic nucleus reuniens (NR) is necessary to extinguish contextu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42429-6 |
| _version_ | 1827709644923994112 |
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| author | Heather C. Ratigan Seetha Krishnan Shai Smith Mark E. J. Sheffield |
| author_facet | Heather C. Ratigan Seetha Krishnan Shai Smith Mark E. J. Sheffield |
| author_sort | Heather C. Ratigan |
| collection | DOAJ |
| description | Abstract The adaptive regulation of fear memories is a crucial neural function that prevents inappropriate fear expression. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic nucleus reuniens (NR) is necessary to extinguish contextual fear and innervates hippocampal CA1. However, the role of the NR-CA1 pathway in contextual fear is unknown. We developed a head-restrained virtual reality CFC paradigm, and demonstrate that mice can acquire and extinguish context-dependent fear responses. We found that inhibiting the NR-CA1 pathway following CFC lengthens the duration of fearful freezing epochs, increases fear generalization, and delays fear extinction. Using in vivo imaging, we recorded NR-axons innervating CA1 and found that NR-axons become tuned to fearful freezing following CFC. We conclude that the NR-CA1 pathway actively suppresses fear by disrupting contextual fear memory retrieval in CA1 during fearful freezing behavior, a process that also reduces fear generalization and accelerates extinction. |
| first_indexed | 2024-03-10T17:24:49Z |
| format | Article |
| id | doaj.art-e0f28241f62f48a8bc16f347c3b5287e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:24:49Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e0f28241f62f48a8bc16f347c3b5287e2023-11-20T10:13:26ZengNature PortfolioNature Communications2041-17232023-10-0114111710.1038/s41467-023-42429-6A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discriminationHeather C. Ratigan0Seetha Krishnan1Shai Smith2Mark E. J. Sheffield3Department of Neurobiology, University of ChicagoDepartment of Neurobiology, University of ChicagoDepartment of Neurobiology, University of ChicagoDepartment of Neurobiology, University of ChicagoAbstract The adaptive regulation of fear memories is a crucial neural function that prevents inappropriate fear expression. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic nucleus reuniens (NR) is necessary to extinguish contextual fear and innervates hippocampal CA1. However, the role of the NR-CA1 pathway in contextual fear is unknown. We developed a head-restrained virtual reality CFC paradigm, and demonstrate that mice can acquire and extinguish context-dependent fear responses. We found that inhibiting the NR-CA1 pathway following CFC lengthens the duration of fearful freezing epochs, increases fear generalization, and delays fear extinction. Using in vivo imaging, we recorded NR-axons innervating CA1 and found that NR-axons become tuned to fearful freezing following CFC. We conclude that the NR-CA1 pathway actively suppresses fear by disrupting contextual fear memory retrieval in CA1 during fearful freezing behavior, a process that also reduces fear generalization and accelerates extinction.https://doi.org/10.1038/s41467-023-42429-6 |
| spellingShingle | Heather C. Ratigan Seetha Krishnan Shai Smith Mark E. J. Sheffield A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination Nature Communications |
| title | A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination |
| title_full | A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination |
| title_fullStr | A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination |
| title_full_unstemmed | A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination |
| title_short | A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination |
| title_sort | thalamic hippocampal ca1 signal for contextual fear memory suppression extinction and discrimination |
| url | https://doi.org/10.1038/s41467-023-42429-6 |
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