The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity
dc.contributor.author | Masella, Gianluca | |
dc.contributor.author | Silva, Francisca | |
dc.contributor.author | Cort, Elisa | |
dc.contributor.author | Azkona Mendoza, Garikoitz ![]() | |
dc.contributor.author | Madeira, Maria Francisca | |
dc.contributor.author | Tomé, Angelo R. | |
dc.contributor.author | Ferreira, Samira G. | |
dc.contributor.author | Cunha, Rodrigo A. | |
dc.contributor.author | Duarte, Carlos B. | |
dc.contributor.author | Santos, Monica | |
dc.date.accessioned | 2024-03-27T15:55:17Z | |
dc.date.available | 2024-03-27T15:55:17Z | |
dc.date.issued | 2024-01-17 | |
dc.identifier.citation | Molecular Psychiatry : (2024) | es_ES |
dc.identifier.issn | 13594184 | |
dc.identifier.uri | http://hdl.handle.net/10810/66517 | |
dc.description.abstract | Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, which neurobiological basis is unknown. We characterized a model of extinction learning, whereby fear-conditioned mice were categorized as extinction (EXT)-success or EXT-failure, according to their inherent ability to extinguish fear. In the lateral amygdala, GluN2A-containing NMDAR are required for LTP and stabilization of fear memories, while GluN2B-containing NMDAR are required for LTD and fear extinction. EXT-success mice showed attenuated LTP, strong LTD and higher levels of synaptic GluN2B, while EXT-failure mice showed strong LTP, no LTD and higher levels of synaptic GluN2A. Neurotrophin 3 (NT3) infusion in the lateral amygdala was sufficient to rescue extinction deficits in EXT-failure mice. Mechanistically, activation of tropomyosin receptor kinase C (TrkC) with NT3 in EXT-failure slices attenuated lateral amygdala LTP, in a GluN2B-dependent manner. Conversely, blocking endogenous NT3-TrkC signaling with TrkC-Fc chimera in EXT-success slices strengthened lateral amygdala LTP. Our data support a key role for the NT3-TrkC system in inter-individual differences in fear extinction in rodents, through modulation of amygdalar NMDAR composition and synaptic plasticity. | es_ES |
dc.description.sponsorship | This work was supported by Bial Foundation (grant 85/18) to Mónica Santos and by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01–0145-FEDER-000008/03127 and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, under projects UIDB/04539/2020, UIDP/04539/2020 and LA/P/0058/2020 to all authors. GM and FS were supported by FCT PhD fellowships (2021.06144.BD and 2022.13190.BD, respectively). EC was supported by the H2020-MSCA-ITN-2018 program (grant agreement #813986) and FCT PhD fellowship (2021.08008.BD). GA was supported by a UPV/EHU mobility grant (MOV21/17). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/813986 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2024, The Author(s). 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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. | es_ES |
dc.relation.publisherversion | https://www.nature.com/articles/s41380-024-02412-z | es_ES |
dc.identifier.doi | 10.1038/s41380-024-02412-z | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Procesos psicológicos básicos y su desarrollo | es_ES |
dc.departamentoeu | Oinarrizko psikologia prozesuak eta haien garapena | es_ES |
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Except where otherwise noted, this item's license is described as © 2024, The Author(s). 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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.