Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning
- Yale University, United States
- New York University School of Medicine, United States
- Texas Christian University, United States
- Yale University School of Medicine, United States
Abstract
It is currently unclear whether early life stress (ELS) affects males and females differently. However, a growing body of work has shown that sex moderates responses to stress and injury, with important insights into sex-specific mechanisms provided by work in rodents. Unfortunately, most of the ELS studies in rodents were conducted only in males, a bias that is particularly notable in translational work that has used human imaging. Here we examine the effects of unpredictable postnatal stress (UPS), a mouse model of complex ELS, using high resolution diffusion magnetic resonance imaging. We show that UPS induces several neuroanatomical alterations that were seen in both sexes and resemble those reported in humans. In contrast, exposure to UPS induced fronto-limbic hyper-connectivity in males, but either no change or hypoconnectivity in females. Moderated-mediation analysis found that these sex-specific changes are likely to alter contextual freezing behavior in males but not in females.
Data availability
All imaging data were despited at https://doi.org/10.35092/yhjc.12367658
Article and author information
Author details
Funding
National Institute of Mental Health (R01MH119164)
- Jiangyang Zhang
- Arie Kaffman
National Institute of Mental Health (R01MH118332)
- Jiangyang Zhang
- Arie Kaffman
National Center for Advancing Translational Sciences (TL1 TR001864)
- Jordon D White
National Institute of Neurological Disorders and Stroke (R01NS102904)
- Jiangyang Zhang
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 studies were approved by the Institutional Animal Care and Use Committee (IACUC) at Yale University, protocol #2020-10981, and were conducted in accordance with the recommendations of the NIH Guide for the Care and the Use of Laboratory Animals.
Copyright
© 2020, White 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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Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning
eLife 9:e58301.
https://doi.org/10.7554/eLife.58301
