Sex-specific exploration accounts for differences in valence learning in male and female mice
- McGill University, Canada
Abstract
Valence, the quality by which something is perceived as good or bad, appetitive or aversive, is a fundamental building block of emotional experience and a primary driver of adaptive behavior. Pavlovian fear and reward learning paradigms are widely used in preclinical research to probe mechanisms of valence learning but with limited consideration of sex as a biological variable despite known sex differences in neuropsychiatric disorders associated with impaired valence. Here, we compare appetitive-only, aversive-only and mixed-valence cue-outcome Pavlovian conditioning paradigms in male and female mice to dissociate effects of context, valence and salience in a sex-specific manner. Using a data-driven approach to identify behaviors indicative of valence learning in an unbiased manner, we compare task performance between paradigms in male and female mice. We show that while male and female mice acquire appetitive and aversive associations in both single- and mixed-valence paradigms, sex differences emerge in single-valence paradigms. Ultimately, we show that these apparent sex differences in valence learning are driven by non-specific baseline differences in exploratory behavior. Males explore more at baseline, altering their trajectory of cue-reward association acquisition whereas females explore less at baseline, increasing shock facilitated freezing in aversive-only contexts, masking cue discrimination. Overall, our findings illustrate how task design differentially impacts behavioral expression in male and female mice and demonstrate that mixed-valence paradigms afford a more accurate assessment of valence learning in both sexes.
Data availability
All data is available at https://osf.io/4xfz2/. All code for generating figures and statistical analyses is available at https://github.com/heike-s/ValenceProfile.
Article and author information
Author details
Gabrielle Siemonsmeier
Ariel Mandel Weinbaum
Funding
Canadian Institutes of Health Research (#180648)
- Rosemary C Bagot
Santé
- Heike Schuler
Canadian Institutes of Health Research (#195897)
- Rosemary C Bagot
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the Animal Care Committee and conformed to McGill University Comparative Medicine and Animal Resources Centre guidelines.
Copyright
© 2025, Schuler et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Sex-specific exploration accounts for differences in valence learning in male and female mice
eLife 14:e108498.
https://doi.org/10.7554/eLife.108498
