History of winning and hierarchy landscape influence stress susceptibility in mice

  1. Katherine B LeClair
  2. Kenny L Chan
  3. Manuella P Kaster
  4. Lyonna F Parise
  5. Charles Joseph Burnett
  6. Scott Russo  Is a corresponding author
  1. Icahn School of Medicine at Mount Sinai, United States
  2. Federal University of Santa Catarina, Brazil

Abstract

Social hierarchy formation is strongly evolutionarily conserved. Across species, rank within social hierarchy has large effects on health and behavior. To investigate the relationship between social rank and stress susceptibility, we exposed ranked male and female mice to social and non-social stressors and manipulated social hierarchy position. We found that rank predicts same sex social stress outcomes: dominance in males and females confers resilience while subordination confers susceptibility. Pre-existing rank does not predict non-social stress outcomes in females and weakly does so in males, but rank emerging under stress conditions reveals social interaction deficits in male and female subordinates. Both history of winning and rank of cage mates affect stress susceptibility in males: rising to the top rank through high mobility confers resilience and mice that lose dominance lose stress resilience, though gaining dominance over a subordinate animal does not confer resilience. Overall, we have demonstrated a relationship between social status and stress susceptibility, particularly when taking into account individual history of winning and the overall hierarchy landscape in male and female mice.

Data availability

All data generated or analyzed during this study are included in the manuscript.

Article and author information

Author details

  1. Katherine B LeClair

    Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kenny L Chan

    Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Manuella P Kaster

    Federal University of Santa Catarina, Santa Catarina, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Lyonna F Parise

    Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Charles Joseph Burnett

    Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Scott Russo

    Icahn School of Medicine at Mount Sinai, New York, United States
    For correspondence
    scott.russo@mssm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6470-1805

Funding

National Institutes of Health (R01MH114882)

  • Scott Russo

National Institutes of Health (R01MH127820)

  • Scott Russo

National Institutes of Health (R01MH104559)

  • Scott Russo

CAPES-Brazil (Visiting Researcher Fellowship)

  • Manuella P Kaster

Canadian Institutes of Health Research (Postdoctoral Fellowship,201811MFE-414896-231226)

  • Kenny L Chan

Leon Levy Foundation (Postdoctoral Fellowship)

  • Lyonna F Parise

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Rebecca Shansky, Northeastern University, United States

Ethics

Animal experimentation: All animal procedures were approved by the Icahn School of Medicine at Mount SinaiInstitutional Animal Care and Use Committee (Protocol #: LA10-00266 to S.J.R.)

Version history

  1. Received: June 18, 2021
  2. Preprint posted: July 7, 2021 (view preprint)
  3. Accepted: September 27, 2021
  4. Accepted Manuscript published: September 28, 2021 (version 1)
  5. Version of Record published: October 7, 2021 (version 2)

Copyright

© 2021, LeClair 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

  • 2,372
    views
  • 380
    downloads
  • 27
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Katherine B LeClair
  2. Kenny L Chan
  3. Manuella P Kaster
  4. Lyonna F Parise
  5. Charles Joseph Burnett
  6. Scott Russo
(2021)
History of winning and hierarchy landscape influence stress susceptibility in mice
eLife 10:e71401.
https://doi.org/10.7554/eLife.71401

Share this article

https://doi.org/10.7554/eLife.71401

Further reading

    1. Neuroscience
    Ladan Shahshahani, Maedbh King ... Jörn Diedrichsen
    Research Article

    Functional magnetic resonance imaging (fMRI) studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here, we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.

    1. Neuroscience
    Petteri Stenroos, Isabelle Guillemain ... Emmanuel L Barbier
    Research Article

    In patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. Absence seizures are characterized by spike-and-wave discharges on the electroencephalogram associated with a transient alteration of consciousness. However, it is still unknown how the brain responds to external stimuli during and outside of seizures. This study aimed to investigate responsiveness to visual and somatosensory stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established rat model for absence epilepsy. Animals were imaged under non-curarized awake state using a quiet, zero echo time, functional magnetic resonance imaging (fMRI) sequence. Sensory stimulations were applied during interictal and ictal periods. Whole-brain hemodynamic responses were compared between these two states. Additionally, a mean-field simulation model was used to explain the changes of neural responsiveness to visual stimulation between states. During a seizure, whole-brain responses to both sensory stimulations were suppressed and spatially hindered. In the cortex, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The mean-field simulation revealed restricted propagation of activity due to stimulation and agreed well with fMRI findings. Results suggest that sensory processing is hindered or even suppressed by the occurrence of an absence seizure, potentially contributing to decreased responsiveness during this absence epileptic process.