Extinction of contextual fear memory is facilitated in TRPM2 knockout mice
Abstract Transient receptor potential melastatin type 2 (TRPM2) is a nonselective cation channel involved in synaptic plasticity. We investigated its role in contextual fear conditioning and extinction of conditioned fear using Trpm2-deficient (Trpm2 −/− ) mice. Trpm2 −/− mice exhibited reduced acqu...
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| Language: | English |
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BMC
2025-02-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-025-01181-2 |
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| author | Seung Yeon Ko Do Gyeong Kim Huiju Lee Sung Jun Jung Hyeon Son |
| author_facet | Seung Yeon Ko Do Gyeong Kim Huiju Lee Sung Jun Jung Hyeon Son |
| author_sort | Seung Yeon Ko |
| collection | DOAJ |
| description | Abstract Transient receptor potential melastatin type 2 (TRPM2) is a nonselective cation channel involved in synaptic plasticity. We investigated its role in contextual fear conditioning and extinction of conditioned fear using Trpm2-deficient (Trpm2 −/− ) mice. Trpm2 −/− mice exhibited reduced acquisition of contextual fear memory during conditioning but had an intact freezing response to conditioning context 24 h after conditioning. They also showed a reduced freezing response to extinction training, indicating facilitated extinction. Consistent with this, infusion of flufenamic acid (FFA), a TRPM2 antagonist, into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. The enhanced extinction in Trpm2 −/− and FFA-treated mice was associated with down-regulation of immediate-early genes (IEGs) including Npas4, c-Fos, Arc and Egr1 in the hippocampus after extinction training. Our results indicate that TRPM2 plays a positive role in retention of contextual fear memory by modulating neuronal activity in the hippocampus, and suggest that TRPM2 activity could potentially be targeted to strengthen extinction-based exposure therapies for post-traumatic stress disorder (PTSD). |
| format | Article |
| id | doaj-art-c16091b67c994826bdb7e6712e54accc |
| institution | OA Journals |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Molecular Brain |
| spelling | doaj-art-c16091b67c994826bdb7e6712e54accc2025-08-20T02:27:14ZengBMCMolecular Brain1756-66062025-02-0118111210.1186/s13041-025-01181-2Extinction of contextual fear memory is facilitated in TRPM2 knockout miceSeung Yeon Ko0Do Gyeong Kim1Huiju Lee2Sung Jun Jung3Hyeon Son4Hanyang Biomedical Research Institute, Hanyang UniversityGraduate School of Biomedical Science and Engineering, Hanyang UniversityGraduate School of Biomedical Science and Engineering, Hanyang UniversityDepartment of Physiology, College of Medicine, Hanyang UniversityHanyang Biomedical Research Institute, Hanyang UniversityAbstract Transient receptor potential melastatin type 2 (TRPM2) is a nonselective cation channel involved in synaptic plasticity. We investigated its role in contextual fear conditioning and extinction of conditioned fear using Trpm2-deficient (Trpm2 −/− ) mice. Trpm2 −/− mice exhibited reduced acquisition of contextual fear memory during conditioning but had an intact freezing response to conditioning context 24 h after conditioning. They also showed a reduced freezing response to extinction training, indicating facilitated extinction. Consistent with this, infusion of flufenamic acid (FFA), a TRPM2 antagonist, into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. The enhanced extinction in Trpm2 −/− and FFA-treated mice was associated with down-regulation of immediate-early genes (IEGs) including Npas4, c-Fos, Arc and Egr1 in the hippocampus after extinction training. Our results indicate that TRPM2 plays a positive role in retention of contextual fear memory by modulating neuronal activity in the hippocampus, and suggest that TRPM2 activity could potentially be targeted to strengthen extinction-based exposure therapies for post-traumatic stress disorder (PTSD).https://doi.org/10.1186/s13041-025-01181-2Transient receptor potential melastatin type 2 (TRPM2)ExtinctionFear memory |
| spellingShingle | Seung Yeon Ko Do Gyeong Kim Huiju Lee Sung Jun Jung Hyeon Son Extinction of contextual fear memory is facilitated in TRPM2 knockout mice Molecular Brain Transient receptor potential melastatin type 2 (TRPM2) Extinction Fear memory |
| title | Extinction of contextual fear memory is facilitated in TRPM2 knockout mice |
| title_full | Extinction of contextual fear memory is facilitated in TRPM2 knockout mice |
| title_fullStr | Extinction of contextual fear memory is facilitated in TRPM2 knockout mice |
| title_full_unstemmed | Extinction of contextual fear memory is facilitated in TRPM2 knockout mice |
| title_short | Extinction of contextual fear memory is facilitated in TRPM2 knockout mice |
| title_sort | extinction of contextual fear memory is facilitated in trpm2 knockout mice |
| topic | Transient receptor potential melastatin type 2 (TRPM2) Extinction Fear memory |
| url | https://doi.org/10.1186/s13041-025-01181-2 |
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