1. Neuroscience
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Stimulus salience determines defensive behaviors elicited by aversively conditioned serial compound auditory stimuli

  1. Sarah Hersman
  2. David Allen
  3. Mariko Hashimoto
  4. Salvador Ignacio Brito
  5. Todd E Anthony  Is a corresponding author
  1. Children's Hospital Boston, United States
Research Article
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Cite this article as: eLife 2020;9:e53803 doi: 10.7554/eLife.53803

Abstract

Assessing the imminence of threatening events using environmental cues enables proactive engagement of appropriate avoidance responses. The neural processes employed to anticipate event occurrence depend upon which cue properties are used to formulate predictions. In serial compound stimulus (SCS) conditioning in mice, repeated presentations of sequential tone (CS1) and white noise (CS2) auditory stimuli immediately prior to an aversive event (US) produces freezing and flight responses to CS1 and CS2, respectively (Fadok et al., 2017). Recent work reported that these responses reflect learned temporal relationships of CS1 and CS2 to the US (Dong et al., 2019). However, we find that frequency and sound pressure levels, not temporal proximity to the US, are the key factors underlying SCS-driven conditioned responses. Moreover, white noise elicits greater physiological and behavioral responses than tones even prior to conditioning. Thus, stimulus salience is the primary determinant of behavior in the SCS paradigm, and represents a potential confound in experiments utilizing multiple sensory stimuli.

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 in MS Excel format, with primary measurements in one file and statistical analyses in another file.

Article and author information

Author details

  1. Sarah Hersman

    Psychiatry and Neurology, Children's Hospital Boston, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. David Allen

    Psychiatry and Neurology, Children's Hospital Boston, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mariko Hashimoto

    Psychiatry and Neurology, Children's Hospital Boston, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Salvador Ignacio Brito

    Psychiatry and Neurology, Children's Hospital Boston, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Todd E Anthony

    Psychiatry and Neurology, Children's Hospital Boston, Boston, United States
    For correspondence
    todd.anthony@childrens.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7284-7556

Funding

National Institutes of Health (1R01MH117421-01A1)

  • Todd E Anthony

National Institutes of Health (T32 NS007473)

  • Sarah Hersman

Whitehall Foundation (2016-05-99)

  • Todd E Anthony

Charles H. Hood Foundation (2017-10-1)

  • Todd E Anthony

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

Ethics

Animal experimentation: The behavioral procedures used in this study were 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 animals were handled according to protocols approved by the institutional animal care and use committee (IACUC) at Boston Children's Hospital (Protocol 18-07-3726R).

Reviewing Editor

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

Publication history

  1. Received: November 21, 2019
  2. Accepted: March 26, 2020
  3. Accepted Manuscript published: March 27, 2020 (version 1)
  4. Version of Record published: April 29, 2020 (version 2)

Copyright

© 2020, Hersman 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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