A prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat
- NIH, United States
- Santa Clara University, United States
Abstract
In many cases of trauma, the same environmental stimuli that become associated with aversive events are experienced on other occasions without adverse consequence. We examined neural circuits underlying partially reinforced fear (PRF), whereby mice received tone-shock pairings on half of conditioning trials. Tone-elicited freezing was lower after PRF conditioning than fully reinforced fear (FRF) conditioning, despite an equivalent number of tone-shock pairings. PRF preferentially activated medial prefrontal cortex (mPFC) and bed nucleus of the stria terminalis (BNST). Chemogenetic inhibition of BNST-projecting mPFC neurons increased PRF, not FRF, freezing. Multiplexing chemogenetics with in vivo neuronal recordings showed elevated infralimbic cortex (IL) neuronal activity during CS-onset and freezing-cessation; these neural correlates were abolished by chemogenetic mPFC®BNST inhibition. These data suggest mPFC®BNST neurons limit fear to threats with a history of partial association with an aversive stimulus, with potential implications for understanding the neural basis of trauma-related disorders.
Data availability
Some of the data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1.
Article and author information
Author details
Funding
National Institute on Alcohol Abuse and Alcoholism (NIAAA-IRP)
- Andrew Holmes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mihaela D Iordanova, Concordia University, Canada
Ethics
Animal experimentation: All experimental procedures were approved by the NIAAA (protocol # LBGN-AH-01) and Santa Clara University (SCU AWA: D18-01042) Animal Care and Use Committees and followed the NIH guidelines outlined in 'Using Animals in Intramural Research' and the local Animal Care and Use Committees.
Version history
- Received: July 7, 2020
- Accepted: December 11, 2020
- Accepted Manuscript published: December 15, 2020 (version 1)
- Version of Record published: February 22, 2021 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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A prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat
eLife 9:e60812.
https://doi.org/10.7554/eLife.60812
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