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Environmental enrichment rescues survival and function of adult-born neurons following early life stress

Molecular Psychiatry volume 26, pages 1898–1908 (2021)Cite this article

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Abstract

Adverse experiences early in life are associated with the development of psychiatric illnesses. The hippocampus is likely to play pivotal role in generating these effects: it undergoes significant development during childhood and is extremely reactive to stress. In rodent models, stress in the pre-pubertal period impairs adult hippocampal neurogenesis (AHN) and behaviours which rely on this process. In normal adult animals, environmental enrichment (EE) is a potent promoter of AHN and hippocampal function. Whether exposure to EE during adolescence can restore normal hippocampal function and AHN following pre-pubertal stress (PPS) is unknown. We investigated EE as a treatment for reduced AHN and hippocampal function following PPS in a rodent model. Stress was administered between post-natal days (PND) 25–27, EE from PND 35 to early adulthood, when behavioural testing and assessment of AHN took place. PPS enhanced fear reactions to a conditioned stimulus (CS) following a trace fear protocol and reduced the survival of 4-week-old adult-born neurons throughout the adult hippocampus. Furthermore, we show that fewer adult-born neurons were active during recall of the CS stimulus following PPS. All effects were reversed by EE. Our results demonstrate lasting effects of PPS on the hippocampus and highlight the utility of EE during adolescence for restoring normal hippocampal function. EE during adolescence is a promising method of enhancing impaired hippocampal function resulting from early life stress, and due to multiple benefits (low cost, few side effects, widespread availability) should be more thoroughly explored as a treatment option in human sufferers of childhood adversity.

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Fig. 1: Freezing behavior on the training day.
Fig. 2: Context and CS recall.
Fig. 3: Survival and activity of adult-born neurons.
Fig. 4: Correlation between freezing behavior and adult-born neurons.

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Acknowledgements

We wish to acknowledge support from the Cardiff University Neuroscience and Mental Health Research Institute and The Jane Hodge Foundation who provided NMB with fellowship funding during this research.

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  1. Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK

    Lowenna Rule, Jessica Yang, Holly Watkin, Jeremy Hall & Nichola Marie Brydges

  2. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK

    Jeremy Hall

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Rule, L., Yang, J., Watkin, H. et al. Environmental enrichment rescues survival and function of adult-born neurons following early life stress. Mol Psychiatry 26, 1898–1908 (2021). https://doi.org/10.1038/s41380-020-0718-4

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