Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals
- Texas A&M University, United States
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.
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All data generated or analyses during this study are included in the manuscript and supporting files.
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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.
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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Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals
eLife 8:e46525.
https://doi.org/10.7554/eLife.46525
