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A Daily Injection Paradigm Disrupts the Environmental-Enrichment-Induced Pruning of Miswired Axonal Projections in
Lara Rogerson-Wood1, Atomu Sawatari1, Claire S Goldsbury1
1Neuroscience, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Developmental Neurobiology
|January 13, 2026
Summary
Environmental enrichment (EE) can repair brain wiring in mice, but the injection procedure disrupted this microglial-mediated repair. This highlights the sensitivity of EE-driven circuit correction and the need for careful experimental controls.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Environmental enrichment (EE) shows potential for treating neurodevelopmental conditions by altering brain circuitry.
- Microglia, immune cells in the brain, are implicated in experience-dependent circuit refinement.
- Previous work demonstrated EE partially repairs retinal projections in Ten-m3 knockout (KO) mice, linked to microglial activity.
Purpose of the Study:
- To investigate the causal role of microglial-mediated engulfment in EE-driven circuit repair.
- To assess the impact of minocycline, a microglial inhibitor, on microglial reactivity and retinal projection pruning in Ten-m3 KO mice.
Main Methods:
- Ten-m3 KO mice received daily injections of minocycline or vehicle from postnatal day 18 to 24.
- Microglial reactivity and anatomical pruning of retinal projections were assessed at postnatal day 25.
- Environmental enrichment was applied to assess its effect on these measures.
Main Results:
- Environmental enrichment effects were observed, but both vehicle and minocycline treatments abolished microglial reactivity.
- A marked absence of corrective pruning of miswired retinal projections was noted in both treated groups.
- The injection procedure itself appeared to disrupt the experience-induced microglial-mediated circuit repair.
Conclusions:
- The findings suggest that the experimental procedure interfered with EE-driven microglial-mediated circuit repair.
- Microglial-driven corrective pruning is highly sensitive to experimental manipulations.
- Careful consideration and control of all aspects of experience are crucial in studies of EE and neurodevelopment.
