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Proc Natl Acad Sci U S A. 2016 Oct 25. pii: 201606351. [Epub ahead of print]

Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex.

Author information

1
Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
2
Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
3
Laboratory of Psychology, Jichi Medical University, Tochigi 329-0498, Japan.
4
Department of Integrative Aging Neuroscience, National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan.
5
Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; takahast@yokohama-cu.ac.jp.

Abstract

Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life.

KEYWORDS:

AMPA receptor trafficking; actin dynamics; medial prefrontal cortex; social dominance; social isolation stress

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