Stimulus salience determines defensive behaviors elicited by aversively conditioned serial compound auditory stimuli
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.
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
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.
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).
- Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States
- Received: November 21, 2019
- Accepted: March 26, 2020
- Accepted Manuscript published: March 27, 2020 (version 1)
- Version of Record published: April 29, 2020 (version 2)
© 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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