Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo

Conor Liston; Wen-Biao Gan

doi:10.1073/pnas.1110444108

journal article Sep 12, 2011

Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo

Conor Liston

Wen-Biao Gan

Proceedings of the National Academy of Sciences Vol. 108 No. 38 pp. 16074-16079 · Proceedings of the National Academy of Sciences

View at Publisher Save 10.1073/pnas.1110444108

Abstract

Glucocorticoids are a family of hormones that coordinate diverse physiological processes in responding to stress. Prolonged glucocorticoid exposure over weeks has been linked to dendritic atrophy and spine loss in fixed tissue studies of adult brains, but it is unclear how glucocorticoids may affect the dynamic processes of dendritic spine formation and elimination in vivo. Furthermore, relatively few studies have examined the effects of stress and glucocorticoids on spines during the postnatal and adolescent period, which is characterized by rapid synaptogenesis followed by protracted synaptic pruning. To determine whether and to what extent glucocorticoids regulate dendritic spine development and plasticity, we used transcranial two-photon microscopy to track the formation and elimination of dendritic spines in vivo after treatment with glucocorticoids in developing and adult mice. Corticosterone, the principal murine glucocorticoid, had potent dose-dependent effects on dendritic spine dynamics, increasing spine turnover within several hours in the developing barrel cortex. The adult barrel cortex exhibited diminished baseline spine turnover rates, but these rates were also enhanced by corticosterone. Similar changes occurred in multiple cortical areas, suggesting a generalized effect. However, reducing endogenous glucocorticoid activity by dexamethasone suppression or corticosteroid receptor antagonists caused a substantial reduction in spine turnover rates, and the former was reversed by corticosterone replacement. Notably, we found that chronic glucocorticoid excess led to an abnormal loss of stable spines that were established early in life. Together, these findings establish a critical role for glucocorticoids in the development and maintenance of dendritic spines in the living cortex.

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Details

Published: Sep 12, 2011
Vol/Issue: 108(38)
Pages: 16074-16079

Authors

C

Conor Liston

Molecular Neurobiology Program, Skirball Institute, Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016; and; Department of Psychiatry, Weill Cornell Medical College, New York, NY 10021

W

Wen-Biao Gan

Molecular Neurobiology Program, Skirball Institute, Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016; and

Cite This Article

Conor Liston, Wen-Biao Gan (2011). Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proceedings of the National Academy of Sciences, 108(38), 16074-16079. https://doi.org/10.1073/pnas.1110444108

Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo

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