Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Blog
    • Collections
    • Podcast
  • TOPICS
    • Cognition and Behavior
    • Development
    • Disorders of the Nervous System
    • History, Teaching and Public Awareness
    • Integrative Systems
    • Neuronal Excitability
    • Novel Tools and Methods
    • Sensory and Motor Systems
  • ALERTS
  • FOR AUTHORS
  • ABOUT
    • Overview
    • Editorial Board
    • For the Media
    • Privacy Policy
    • Contact Us
    • Feedback
  • SUBMIT

User menu

Search

  • Advanced search
eNeuro

eNeuro

Advanced Search

 

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Blog
    • Collections
    • Podcast
  • TOPICS
    • Cognition and Behavior
    • Development
    • Disorders of the Nervous System
    • History, Teaching and Public Awareness
    • Integrative Systems
    • Neuronal Excitability
    • Novel Tools and Methods
    • Sensory and Motor Systems
  • ALERTS
  • FOR AUTHORS
  • ABOUT
    • Overview
    • Editorial Board
    • For the Media
    • Privacy Policy
    • Contact Us
    • Feedback
  • SUBMIT
PreviousNext
Research ArticleResearch Article: New Research, Cognition and Behavior

Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice

Hibiki Okamura, Shinnosuke Yasugaki, Haruka Suzuki-Abe, Yoshifumi Arai, Katsuyasu Sakurai, Masashi Yanagisawa, Hotaka Takizawa and Yu Hayashi
eNeuro 18 April 2022, 9 (3) ENEURO.0068-22.2022; DOI: https://doi.org/10.1523/ENEURO.0068-22.2022
Hibiki Okamura
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
2PhD Program in Humanics, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinnosuke Yasugaki
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
3Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
4Research Fellow of Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, 102-0083, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haruka Suzuki-Abe
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
5Research and Development Center for Precision Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshifumi Arai
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
6Master’s Program in Medical Science, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katsuyasu Sakurai
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masashi Yanagisawa
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Masashi Yanagisawa
Hotaka Takizawa
7Faculty of Engineering, Information and Systems, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yu Hayashi
1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
8Department of Human Health Science, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yu Hayashi
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Extended Data
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    BALB/c mice exhibit altered behavioral phenotypes immediately and two weeks after repeated SDS. A, Experimental timeline of repeated SDS. B, Body weight change on day 8 (left) and daily body weight change during the 7 d of SDS (right). C, Schematic of the SIT arena. D, Comparison of time spent in the avoidance and interaction zones during the SIT_0W between control and defeated mice (top), or among the three groups, stratifying defeated mice into nonavoidant and avoidant mice (bottom). E, Comparison of time spent in the open arms and the total distance during EPM_0W between control and defeated mice (top), or among the three groups (bottom). F, Comparison of time spent in the avoidance and interaction zones during the SIT_2W between control and defeated mice (top), or among the three groups (bottom). G, Comparison of time spent in the open arms and the total distance traveled during EPM_2W between control and defeated mice (top), or compared among the three groups (bottom). Control mice: n = 10, defeated mice: n = 15, data are presented as means ± SEM. B, ***/###p < 0.001, ****/####p < 0.0001, Unpaired t test for comparison between two groups and two-way repeated measures ANOVA followed by multiple comparison tests with Bonferroni correction for daily body weight change. D–G, ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, Unpaired t test with Welch’s correction for comparison between two groups and Welch ANOVA test followed by Games–Howell’s multiple comparisons test for comparison among the three groups. Orange triangles and blue squares indicate nonavoidant mice and avoidant mice in the SIT_0W, respectively. Detailed results of the statistical tests are described in Extended Data Figure 1-1, 2-1, 3-1, 4-1, 6-1.

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2.

    Establishment and evaluation of the semi-automated c-Fos extraction and quantitation method. A, Example of a coronal section that includes the PAG. The pink shadow (left) shows the region outlined as PAG with the semi-automated method (PAG_auto), and the white shadow (middle) shows the PAG region that was manually outlined (PAG_manual). Scale bar: 1 mm. Red dots (right) indicate locations that were detected as c-Fos signals by the semi-automated method. B, The sensitivity and precision for PAG outlining using the semi-automated method. C, Comparison of c-Fos signal densities within PAG quantified either manually or by the semi-automated method, and the scatter plot showing correlations in c-Fos signal densities quantified by the manual and semi-automated methods. D, The sensitivity and precision for c-Fos signal detection within the PAG using the semi-automated method. Control: n = 10, defeat: n = 10 (10 defeated mice were randomly selected from 15 mice). Data are presented as means ± SEM. C, Paired t test and Pearson correlation coefficients. ns, not significant. Detailed results of the statistical tests are described in Extended Data Figure 2-1.

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3.

    Identification of brain regions that exhibit differential activity between the control and defeated mice following social interaction. A–S, Comparison of c-Fos signal densities between control and defeated mice in various brain regions. PAG, periaqueductal gray; NAc, nucleus accumbens; CeA, central amygdala; mPFC, medial prefrontal cortex; VTA, ventral tegmental area; CoA, cortical amygdala; LSv, lateral septal nucleus ventral part; BNST, bed nucleus of the stria terminalis; BLA, basolateral amygdala; DG, dentate gyrus; LHb, lateral habenula; MHb, medial habenula; PBN, parabrachial nucleus; LC, locus coeruleus. Control: n = 10, defeat: n = 15, data are presented as means ± SEM, *p < 0.05, **p < 0.01, unpaired t test. Detailed results of the statistical tests are described in Extended Data Figure 3-1. T–W, Representative images of c-Fos signals in the PAG (T), CeA (U), NAc (V), and mPFC (W) of control and defeated mice. Scale bar: 0.05 mm.

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4.

    Repeated SDS leads to the emergence of an activity correlation between various brain regions. A–ab, Scatter plots showing correlations in c-Fos signal densities among pairs of brain regions that showed altered activity between control and defeated mice in Figure 3. ac, ad, Heatmaps showing the overview of the r and p values of Pearson correlation coefficients. Control: n = 10, defeat: n = 15, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, Pearson correlation coefficients. Detailed results of the statistical tests are described in Extended Data Figure 4-1.

  • Figure 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5.

    Hierarchical cluster analysis of subpopulations of defeated mice based on c-Fos expression following social interaction 18 d after the repeated SDS. Results of two-way hierarchical clustering analysis are shown together with heatmap visualization of normalized c-Fos signal densities. Av_both indicates mice that were avoidant mice in both SIT_0W and SIT_2W. Av_0W and Av_2W indicate mice that were avoidant in either SIT_0W or SIT_2W, respectively. Non-Av indicates mice that were nonavoidant in both SIT_0W and SIT_2W; * shows the brain regions that showed altered activity between control and defeated mice in Figure 3.

  • Figure 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6.

    Identification of brain regions that showed altered c-Fos signal densities among subpopulations of defeated mice following social interaction 18 d after the repeated SDS. A–S, Comparison of c-Fos signal densities among the subpopulations of defeated mice defined in Figure 5. Av_both: n = 4, Av_0W: n = 4, Av_2W: n = 3, Non-Av: n = 4, data are presented as means ± SEM, */#p < 0.05, two-way ANOVA followed by multiple comparison tests with Bonferroni correction. Detailed results of the statistical tests are described in Extended Data Figure 6-1. T, Representative images of c-Fos signals in the LHb of Av_both and Av_2w mice. Scale bar: 0.05 mm.

Extended Data

  • Figures
  • Extended Data 1

    A code for Semi-automated c-Fos extraction and quantitation method. Download Extended Data 1, ZIP file.

  • Extended Data Figure 1-1

    Detailed results of the statistical analyses in Figure 1. Download Figure 1-1, XLS file.

  • Extended Data Figure 2-1

    Detailed results of the statistical analyses in Figure 2. Download Figure 2-1, XLS file.

  • Extended Data Figure 3-1

    Detailed results of the statistical analyses in Figure 3. Download Figure 3-1, XLS file.

  • Extended Data Figure 4-1

    Detailed results of the statistical analyses in Figure 4. Download Figure 4-1, XLS file.

  • Extended Data Figure 6-1

    Detailed results of the statistical analyses in Figure 6. Download Figure 6-1, XLS file.

Back to top

In this issue

eneuro: 9 (3)
eNeuro
Vol. 9, Issue 3
May/June 16
  • Table of Contents
  • Index by author
  • Ed Board (PDF)
Email

Thank you for sharing this eNeuro article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice
(Your Name) has forwarded a page to you from eNeuro
(Your Name) thought you would be interested in this article in eNeuro.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice
Hibiki Okamura, Shinnosuke Yasugaki, Haruka Suzuki-Abe, Yoshifumi Arai, Katsuyasu Sakurai, Masashi Yanagisawa, Hotaka Takizawa, Yu Hayashi
eNeuro 18 April 2022, 9 (3) ENEURO.0068-22.2022; DOI: 10.1523/ENEURO.0068-22.2022

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Share
Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice
Hibiki Okamura, Shinnosuke Yasugaki, Haruka Suzuki-Abe, Yoshifumi Arai, Katsuyasu Sakurai, Masashi Yanagisawa, Hotaka Takizawa, Yu Hayashi
eNeuro 18 April 2022, 9 (3) ENEURO.0068-22.2022; DOI: 10.1523/ENEURO.0068-22.2022
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Significance Statement
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
    • Synthesis
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • c-fos
  • stress

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

Research Article: New Research

  • The Impact of Chemical Fixation on the Microanatomy of Mouse Organotypic Hippocampal Slices
  • Dopamine Receptor Type 2-Expressing Medium Spiny Neurons in the Ventral Lateral Striatum Have a Non-REM Sleep-Induce Function
  • How Sucrose Preference Is Gained and Lost: An In-Depth Analysis of Drinking Behavior during the Sucrose Preference Test in Mice
Show more Research Article: New Research

Cognition and Behavior

  • Dopamine Receptor Type 2-Expressing Medium Spiny Neurons in the Ventral Lateral Striatum Have a Non-REM Sleep-Induce Function
  • How Sucrose Preference Is Gained and Lost: An In-Depth Analysis of Drinking Behavior during the Sucrose Preference Test in Mice
  • Similarities and Distinctions between Cortical Neural Substrates That Underlie Generation of Malevolent Creative Ideas
Show more Cognition and Behavior

Subjects

  • Cognition and Behavior

  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Latest Articles
  • Issue Archive
  • Blog
  • Browse by Topic

Information

  • For Authors
  • For the Media

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
  • Feedback
(eNeuro logo)
(SfN logo)

Copyright © 2023 by the Society for Neuroscience.
eNeuro eISSN: 2373-2822

The ideas and opinions expressed in eNeuro do not necessarily reflect those of SfN or the eNeuro Editorial Board. Publication of an advertisement or other product mention in eNeuro should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in eNeuro.