Post-trauma behavioral phenotype predicts the degree of vulnerability to fear relapse after extinction in male rats
| Autor: | Fanny Demars, Ralitsa Todorova, Gabriel Makdah, Antonin Forestier, Marie-Odile Krebs, Bill P. Godsil, Thérèse M. Jay, Sidney I. Wiener, Marco N. Pompili |
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| Přispěvatelé: | Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, École nationale vétérinaire - Alfort (ENVA), Martinez Rico, Clara, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
[SDV.BA] Life Sciences [q-bio]/Animal biology animal model [SDV.BA]Life Sciences [q-bio]/Animal biology Conditioning Classical vulnerability Fear interindividual differences General Biochemistry Genetics and Molecular Biology Extinction Psychological Rats Phenotype ethological relevance Recurrence fear relapse Animals General Agricultural and Biological Sciences transcriptional profiling |
| Zdroj: | Current Biology-CB Current Biology-CB, 2022, pp.S0960-9822(22)00853-3. ⟨10.1016/j.cub.2022.05.050⟩ |
| ISSN: | 0960-9822 1879-0445 |
| DOI: | 10.1016/j.cub.2022.05.050⟩ |
| Popis: | International audience; Current treatments for trauma-related disorders remain ineffective for many patients.1,2 Fear extinction deficiency is a prominent feature of these diseases,3 and many behavioral treatments rely on extinction training.4,5 However, in many patients, therapy is followed by a relapse of symptoms, and the underpinnings of such interindividual variations in vulnerability to relapse remain unknown.6-8 Here, we modeled interindividual differences in post-therapy fear relapse with an ethologically relevant trauma recovery paradigm. After fear conditioning, male rats underwent fear extinction while foraging in a large enriched arena, permitting the expression of a wide spectrum of behaviors. An automated multidimensional behavioral assessment revealed that post-conditioning fear response profiles clustered into two groups: some animals expressed fear by freezing more, whereas others darted more, as if fleeing from danger. Remarkably, the tendency of an animal to dart or to freeze after CS presentation during the first extinction session was, respectively, associated with stronger or weaker fear renewal. Moreover, genome-wide transcriptional profiling revealed that these groups differentially regulated specific sets of genes, some of which were previously implicated in anxiety and trauma-related disorders. Our results suggest that post-trauma behavioral phenotypes and the associated gene expression landscapes can serve as markers of fear relapse susceptibility and thus may be instrumental for future development of more effective treatments for psychiatric patients. |
| Databáze: | OpenAIRE |
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