Stimulus salience determines defensive behaviors elicited by aversively conditioned serial compound auditory stimuli
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
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).
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.
Metrics
-
- 2,732
- views
-
- 346
- downloads
-
- 33
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Combining electrophysiological, anatomical and functional brain maps reveals networks of beta neural activity that align with dopamine uptake.
-
- Neuroscience
During rest and sleep, memory traces replay in the brain. The dialogue between brain regions during replay is thought to stabilize labile memory traces for long-term storage. However, because replay is an internally-driven, spontaneous phenomenon, it does not have a ground truth - an external reference that can validate whether a memory has truly been replayed. Instead, replay detection is based on the similarity between the sequential neural activity comprising the replay event and the corresponding template of neural activity generated during active locomotion. If the statistical likelihood of observing such a match by chance is sufficiently low, the candidate replay event is inferred to be replaying that specific memory. However, without the ability to evaluate whether replay detection methods are successfully detecting true events and correctly rejecting non-events, the evaluation and comparison of different replay methods is challenging. To circumvent this problem, we present a new framework for evaluating replay, tested using hippocampal neural recordings from rats exploring two novel linear tracks. Using this two-track paradigm, our framework selects replay events based on their temporal fidelity (sequence-based detection), and evaluates the detection performance using each event's track discriminability, where sequenceless decoding across both tracks is used to quantify whether the track replaying is also the most likely track being reactivated.