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Updated: Mar 19, 2026
Chronic Social Defeat Stress in Early Adolescent Male Mice
Published on: January 24, 2025
Altered structural connectome in adolescent socially isolated mice
Cirong Liu1, Yonghui Li2, Timothy J Edwards2
1Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
Adolescent social isolation disrupts brain connectivity, particularly in the orbitofrontal cortex, leading to fear memory deficits and hyperactivity. This study reveals widespread network alterations impacting social development.
Area of Science:
- Neuroscience
- Developmental Psychology
- Systems Biology
Background:
- Social experience is critical for adolescent brain development and plasticity.
- Social isolation in adolescence can impair white matter microstructure in the prefrontal cortex.
- The impact of social isolation may extend beyond single brain regions to affect distributed neural networks.
Purpose of the Study:
- To compare the structural connectomes of adolescent mice subjected to social isolation with those of normally housed controls.
- To investigate the specific brain regions and neural pathways affected by adolescent social isolation.
- To correlate observed connectome changes with behavioral deficits.
Main Methods:
- Diffusion magnetic resonance imaging (dMRI) was used to analyze brain connectomes.
- Tractography-based analyses and histological examinations were performed.
- Behavioral tests assessed fear memory and locomotion.
Main Results:
- Socially isolated mice exhibited an abnormal connectome with increased degree and reduced modularity, small-worldness, and betweenness.
- The dorsolateral orbitofrontal cortex, entorhinal cortex, and perirhinal cortex showed the most significant increase in degree.
- Microstructural changes were identified in forceps minor and lateral-cortical tracts linked to the dorsolateral orbitofrontal cortex.
- Connectome alterations correlated with deficits in fear memory and increased locomotion.
Conclusions:
- Adolescent social isolation induces widespread structural connectome abnormalities.
- The orbitofrontal cortex and its associated neural pathways are particularly vulnerable to social isolation.
- Disruption of these pathways contributes to behavioral impairments observed after social isolation.
