1. Neuroscience
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Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals

  1. Travis D Goode
  2. Reed L Ressler
  3. Gillian M Acca
  4. Olivia W Miles
  5. Stephen Maren  Is a corresponding author
  1. Texas A&M University, United States
Research Article
  • Cited 27
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Cite this article as: eLife 2019;8:e46525 doi: 10.7554/eLife.46525

Abstract

The bed nucleus of the stria terminalis (BNST) has been implicated in conditioned fear and anxiety, but the specific factors that engage the BNST in defensive behaviors are unclear. Here we examined whether the BNST mediates freezing to conditioned stimuli (CSs) that poorly predict the onset of aversive unconditioned stimuli (USs) in rats. Reversible inactivation of the BNST selectively reduced freezing to CSs that poorly signaled US onset (e.g., a backward CS that followed the US), but did not eliminate freezing to forward CSs even when they predicted USs of variable intensity. Additionally, backward (but not forward) CSs selectively increased Fos in the ventral BNST and in BNST-projecting neurons in the infralimbic region of the medial prefrontal cortex (mPFC), but not in the hippocampus or amygdala. These data reveal that BNST circuits regulate fear to unpredictable threats, which may be critical to the etiology and expression of anxiety.

Data availability

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

Article and author information

Author details

  1. Travis D Goode

    Department of Psychological and Brain Sciences, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1432-8894
  2. Reed L Ressler

    Department of Psychological and Brain Sciences, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0514-8269
  3. Gillian M Acca

    Department of Psychological and Brain Sciences, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Olivia W Miles

    Department of Psychological and Brain Sciences, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephen Maren

    Department of Psychological and Brain Sciences, Texas A&M University, College Station, United States
    For correspondence
    maren@tamu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9342-7411

Funding

National Institute of Mental Health (R01MH065961)

  • Stephen Maren

McKnight Endowment Fund for Neuroscience (Memory and Cognitive Disorders Award)

  • Stephen Maren

Brain and Behavior Research Foundation (Distinguished Investigator Grant)

  • Stephen Maren

National Institute of Mental Health (R01MH117852)

  • Stephen Maren

National Institute of Mental Health (F31MH107113)

  • Travis D Goode

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2015-005) of Texas A&M University. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States

Publication history

  1. Received: March 2, 2019
  2. Accepted: March 28, 2019
  3. Accepted Manuscript published: April 4, 2019 (version 1)
  4. Version of Record published: April 9, 2019 (version 2)

Copyright

© 2019, Goode et al.

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.

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