Sex differences in innate and adaptive neural oscillatory patterns link resilience and susceptibility to chronic stress in rats

Sex differences in innate and adaptive neural oscillatory patterns link resilience and susceptibility to chronic stress in rats

J Psychiatry Neurosci 2021;46(2):E258-E270 | PDF | Appendix

Rachel-Karson Thériault, MSc; Joshua D. Manduca, BSc; Melissa L. Perreault, PhD

Background: Major depressive disorder is a chronic illness with a higher incidence in women. Dysregulated neural oscillatory activity is an emerging mechanism thought to underlie major depressive disorder, but whether sex differences in these rhythms contribute to the development of symptoms is unknown.

Methods: We exposed male and female rats to chronic unpredictable stress and characterized them as stress-resilient or stress-susceptible based on behavioural output in the forced swim test and the sucrose preference test. To identify sex-specific neural oscillatory patterns associated with stress response, we recorded local field potentials from the prefrontal cortex, cingulate cortex, nucleus accumbens and dorsal hippocampus throughout stress exposure.

Results: At baseline, female stress-resilient rats innately exhibited higher theta coherence in hippocampal connections compared with stress-susceptible female rats. Following stress exposure, additional oscillatory changes manifested: stress-resilient females were characterized by increased dorsal hippocampal theta power and cortical gamma power, and stress-resilient males were characterized by a widespread increase in high gamma coherence. In stress-susceptible animals, we observed a pattern of increased delta and reduced theta power; the changes were restricted to the cingulate cortex and dorsal hippocampus in males but occurred globally in females. Finally, stress exposure was accompanied by the time-dependent recruitment of specific neural pathways, which culminated in system-wide changes that temporally coincided with the onset of depression-like behaviour.

Limitations: We could not establish causality between the electrophysiological changes and behaviours with the methodology we employed.

Conclusion: Sex-specific neurophysiological patterns can function as early markers for stress vulnerability and the onset of depression-like behaviours in rats.


Submitted Jul. 3, 2020; Revised Sep. 21, 2020; Accepted Oct. 22, 2020

Affiliations: From the department of Molecular and Cellular Biology, University of Guelph, Guelph, Ont., Canada (Thériault, Manduca, Perreault) and the Collaborative Neuroscience Program, University of Guelph, Guelph, Ont., Canada (Thériault, Perreault).

Funding: This research was supported by the Canadian Institutes of Health Research (grant number 450186 to MLP) and a Vanier Canada Graduate Scholarship (RKT).

Competing interests: None declared.

Contributors: M. Perreault designed the study. R.-K. Thériault and J. Manduca acquired the data, which R.-K. Thériault and M. Perrault analyzed. R.-K. Thériault wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BYNC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

DOI: 10.1503/jpn.200117

Correspondence to: M. L. Perreault, Department of Molecular and Cellular Biology, 50 Stone Rd. E., University of Guelph, Guelph, ON, N1G 2W1; perreaum@uoguelph.ca