Different methods of fear reduction are supported by distinct cortical substrates

Abstract
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Abstract

Understanding how learned fear can be reduced is at the heart of treatments for anxiety disorders. Tremendous progress has been made in this regard through extinction training in which the aversive outcome is omitted. However, current progress almost entirely rests on this single paradigm, resulting in a very specialized knowledgebase at the behavioural and neural level of analysis. Here, we used a dual-paradigm approach to show that different methods that lead to reduction in learned fear in rats are dissociated in the cortex. We report that the infralimbic cortex has a very specific role in fear reduction that depends on the omission of aversive events but not on overexpectation. The orbitofrontal cortex, a structure generally overlooked in fear, is critical for downregulating fear when novel predictions about upcoming aversive events are generated, such as when fear is inflated or overexpected, but less so when an expected aversive event is omitted.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

Belinda PP Lay

Psychology, Concordia University, Montreal, Canada

Competing interests
No competing interests declared.
Audrey A Pitaru

Psychology, Concordia University, Montreal, Canada

Competing interests
No competing interests declared.
Nathan Boulianne

Psychology, Concordia University, Montreal, Canada

Competing interests
No competing interests declared.
Guillem R Esber

Department of Psychology, Brooklyn College of the City University of New York, New York, United States

Competing interests
No competing interests declared.
Mihaela D Iordanova

Department of Psychology, Concordia University, Montreal, Canada

For correspondence
mihaela.iordanova@concordia.ca

Competing interests
Mihaela D Iordanova, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-6232-448X

Funding

Fonds de Recherche du Québec - Nature et Technologies (2017-NC-198182)

Mihaela D Iordanova

Canadian Institutes of Health Research (Project Grant)

Mihaela D Iordanova

Brain and Behavior Research Foundation (NARSAD grant)

Mihaela D Iordanova

Canada Research Chairs

Mihaela D Iordanova

Fonds de Recherche du Québec - Santé

Belinda PP Lay

Natural Sciences and Engineering Research Council of Canada

Nathan Boulianne

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 experimental procedures were in accordance with the approval granted by the Canadian Council on Animal Care and the Concordia University Animal Care Committee.

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.