Shifting from fear to safety through deconditioning-update

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Abstract

Aversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of 'deconditioning' animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval. Our results indicate that deconditioning-update is more effective than traditional extinction in reducing fear responses; moreover, such effects are long lasting and resistant to renewal and spontaneous recovery. Remarkably, this strategy overcame important boundary conditions for memory updating, such as remote or very strong traumatic memories. The same beneficial effect was found in other types of fear-related memories. Deconditioning was mediated by L-type voltage-gated calcium channels and is consistent with computational accounts of mismatch-induced memory updating. Our results suggest that shifting from fear to safety through deconditioning-update is a promising approach to attenuate traumatic memories.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Bruno Popik

Neurobiology of Memory Lab, Biophysics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Competing interests
The authors declare that no competing interests exist.
Felippe Espinelli Amorim

Institute of Medical Biochemistry Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Competing interests
The authors declare that no competing interests exist.
Olavo B Amaral

Institute of Medical Biochemistry Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Competing interests
The authors declare that no competing interests exist.
Lucas Alvares

Neurobiology of Memory Lab, Biophysics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

For correspondence
lucas.alvares@ufrgs.br

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0472-903X

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico (Universal 2018 - 405100/2018-3))

Lucas Alvares

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (graduate fellowship)

Bruno Popik

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures followed the Brazilian ethical guidelines for animal research set by the National Council for the Control of Experimental Animal Research (CONCEA) and approved by the committee on the Ethics of Animal Experiments of the UFRGS (number 34547).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.