Second-order threat conditioning in the amygdala-posterior piriform cortex network
Abstract Fear, while crucial for survival, is a component of a myriad of psychiatric illnesses in its extreme. Persistent fear memories can form through processes such as second-order conditioning (SOC), during which a second-order conditioned stimulus (CS2) acquires significance by associating with...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08287-2 |
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| author | Tayebeh Sepahvand Tian Qin Zia Hasan Kyron D. Power Samantha J. Carew Negar Nazari Alyssa M. Janes Ali Salman Yue Xia Touati Benoukraf Qi Yuan |
| author_facet | Tayebeh Sepahvand Tian Qin Zia Hasan Kyron D. Power Samantha J. Carew Negar Nazari Alyssa M. Janes Ali Salman Yue Xia Touati Benoukraf Qi Yuan |
| author_sort | Tayebeh Sepahvand |
| collection | DOAJ |
| description | Abstract Fear, while crucial for survival, is a component of a myriad of psychiatric illnesses in its extreme. Persistent fear memories can form through processes such as second-order conditioning (SOC), during which a second-order conditioned stimulus (CS2) acquires significance by associating with a first-order conditioned stimulus (CS1). The neural circuitry underlying SOC, particularly the roles of sensory cortices, remains poorly understood. Here we explore the mechanisms of olfactory SOC in rats, focusing on the basolateral amygdala (BLA) and posterior piriform cortex (pPC). Our results demonstrate that NMDAR-dependent plasticity in both regions is essential for SOC. The BLA mediates the CS2-CS1 association, while the pPC, receiving inputs from the locus coeruleus and BLA, is critical for memory acquisition and retrieval. Single-nucleus multiomics analysis of Fos + ensembles in both regions reveals distinct yet overlapping gene activation profiles in excitatory neurons, accompanied by global chromatin remodeling. These findings highlight the specific yet coordinated roles of these structures in supporting learning and memory. |
| format | Article |
| id | doaj-art-48a8909d2fef48e780a772ac2f8f2bea |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-48a8909d2fef48e780a772ac2f8f2bea2025-08-20T02:05:42ZengNature PortfolioCommunications Biology2399-36422025-06-018111810.1038/s42003-025-08287-2Second-order threat conditioning in the amygdala-posterior piriform cortex networkTayebeh Sepahvand0Tian Qin1Zia Hasan2Kyron D. Power3Samantha J. Carew4Negar Nazari5Alyssa M. Janes6Ali Salman7Yue Xia8Touati Benoukraf9Qi Yuan10Biomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityBiomedical Sciences, Faculty of Medicine, Memorial UniversityAbstract Fear, while crucial for survival, is a component of a myriad of psychiatric illnesses in its extreme. Persistent fear memories can form through processes such as second-order conditioning (SOC), during which a second-order conditioned stimulus (CS2) acquires significance by associating with a first-order conditioned stimulus (CS1). The neural circuitry underlying SOC, particularly the roles of sensory cortices, remains poorly understood. Here we explore the mechanisms of olfactory SOC in rats, focusing on the basolateral amygdala (BLA) and posterior piriform cortex (pPC). Our results demonstrate that NMDAR-dependent plasticity in both regions is essential for SOC. The BLA mediates the CS2-CS1 association, while the pPC, receiving inputs from the locus coeruleus and BLA, is critical for memory acquisition and retrieval. Single-nucleus multiomics analysis of Fos + ensembles in both regions reveals distinct yet overlapping gene activation profiles in excitatory neurons, accompanied by global chromatin remodeling. These findings highlight the specific yet coordinated roles of these structures in supporting learning and memory.https://doi.org/10.1038/s42003-025-08287-2 |
| spellingShingle | Tayebeh Sepahvand Tian Qin Zia Hasan Kyron D. Power Samantha J. Carew Negar Nazari Alyssa M. Janes Ali Salman Yue Xia Touati Benoukraf Qi Yuan Second-order threat conditioning in the amygdala-posterior piriform cortex network Communications Biology |
| title | Second-order threat conditioning in the amygdala-posterior piriform cortex network |
| title_full | Second-order threat conditioning in the amygdala-posterior piriform cortex network |
| title_fullStr | Second-order threat conditioning in the amygdala-posterior piriform cortex network |
| title_full_unstemmed | Second-order threat conditioning in the amygdala-posterior piriform cortex network |
| title_short | Second-order threat conditioning in the amygdala-posterior piriform cortex network |
| title_sort | second order threat conditioning in the amygdala posterior piriform cortex network |
| url | https://doi.org/10.1038/s42003-025-08287-2 |
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