Original Article | Published:

Stress-induced structural plasticity of medial amygdala stellate neurons and rapid prevention by a candidate antidepressant

Molecular Psychiatry volume 22, pages 227234 (2017) | Download Citation

Abstract

The adult brain is capable of adapting to internal and external stressors by undergoing structural plasticity, and failure to be resilient and preserve normal structure and function is likely to contribute to depression and anxiety disorders. Although the hippocampus has provided the gateway for understanding stress effects on the brain, less is known about the amygdala, a key brain area involved in the neural circuitry of fear and anxiety. Here, in mice more vulnerable to stressors, we demonstrate structural plasticity within the medial and basolateral regions of the amygdala in response to prolonged 21-day chronic restraint stress (CRS). Three days before the end of CRS, treatment with the putative, rapidly acting antidepressant, acetyl-l-carnitine (LAC) in the drinking water opposed the direction of these changes. Behaviorally, the LAC treatment during the last part of CRS enhanced resilience, opposing the effects of CRS, as shown by an increased social interaction and reduced passive behavior in a forced swim test. Furthermore, CRS mice treated with LAC show resilience of the CRS-induced structural remodeling of medial amygdala (MeA) stellate neurons. Within the basolateral amygdala (BLA), LAC did not reduce, but slightly enhanced, the CRS-increased length and number of intersections of pyramidal neurons. No structural changes were observed in MeA bipolar neurons, BLA stellate neurons or in lateral amygdala stellate neurons. Our findings identify MeA stellate neurons as an important component in the responses to stress and LAC action and show that LAC can promote structural plasticity of the MeA. This may be useful as a model for increasing resilience to stressors in at-risk populations.

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Acknowledgements

We thank Anjali Ferris for her commitment in blind analyses for structural and behavioral experiments. This work was supported by the AFSP (American Foundation for Suicide Prevention), HDRF (Hope for Depression Research Foundation), NIH Grant RO1 MH41256 and by Grant UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program.

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Affiliations

  1. Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA

    • T Lau
    • , D Zelli
    • , B S McEwen
    •  & C Nasca
  2. Center for Clinical and Translational Science, The Rockefeller University, New York, NY, USA

    • B Bigio

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Competing interests

The authors declare no conflict of interest.

Corresponding authors

Correspondence to B S McEwen or C Nasca.

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DOI

https://doi.org/10.1038/mp.2016.68

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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