Review
Mechanisms underlying epigenetic effects of early social experience: The role of neuropeptides and steroids

https://doi.org/10.1016/j.neubiorev.2005.04.001Get rights and content

Abstract

In mammals the neonatal period is a time of significant social interaction. This is true even in solitary species as females spend a significant amount of time nursing and caring for their offspring. In social species interactions may also include the father, older siblings and extended family members. This period is a time of significant development, including organization of the central nervous system, and therefore a time when the degree and type of social interaction influences the development and expression of social behavior in adulthood. The purpose of this review is to examine the possible mechanisms for the epigenetic effects of early social experience on the subsequent expression of social behavior. We propose that social interactions during the neonatal period organize the subsequent expression of behavior by altering sensitivity to neuropeptides and steroids. Both neuropeptides (e.g. oxytocin and arginine vasopressin) and steroids (e.g. estrogen) regulate or influence the expression of behaviors such as affiliation, aggression, sociosexual behavior, parental behavior, and responses to stress. Therefore, changes in sensitivity to these hormones via reorganization of receptors or changes in hormone production and secretion are potentially powerful mechanisms through which early social experience can mold subsequent social behaviors.

Section snippets

Early social environments and the development of social behavior

The early postnatal period is a critical period when social interactions can affect the development of subsequent adult social behavior (Laviola and Terranova, 1998, Lovic et al., 2001, Ladd et al., 2000, Francis et al., 1999, Chiccetti and Carlson, 1989, Suomi and Ripp, 1983), as it is a time of significant development when major modifications occur in behavior, physiology, and morphology. This period can last from several weeks to months or even years, such as in humans and some other large

Early social experience alters neuroanatomy and neuroendocrine responses

While non-genomic environmental/epigenetic effects frequently are indexed by performance, such as the degree of fearfulness, anxiety, blood pressure, stress response, tests of learning and memory, or the expression of behavior there must be underlying mechanisms that regulate the changes. Early postnatal experiences, especially those that result in long-term changes must be associated with a reorganization or restructuring of the underlying physiological/neuroendocrine mechanisms. Early studies

Neuroendocrine regulation of social behavior

While factors such as context, learning, and memory play a role in the expression of social behavior, social behavior is a product of the underlying mechanisms regulating it. Social behavior often is the product of complex interactions. For example, the development of a long-term bond between two individuals may start with a slow approach and early investigation, which involves overcoming an initial fear or stress response, which may or may not stimulate aggressive interactions. The development

ERα and neuropeptides: Sexually dimorphic social behavior

A comparison of the expression of ERα between males and females reveals a relevant pattern. In rats, where adult male social activity is primarily limited to mating, the expression and distribution of ERα in the brain is similar in males and females (Kawata et al., 1998, Yokosuka et al., 1997, Kuhnemann et al., 1995, Lauber et al., 1991, Simerly et al., 1990). There are, however, some notable exceptions with males expressing significantly less ERα in the medial preoptic area (MPOA) and the

Social behavior and the BST and MeA

Based on extensive overlap in function and interconnections between nuclei in the limbic system (BST, MeA, MPOA, lateral septum (LS), VMH, central amygdala, anterior hypothalamus), it has been proposed that these nuclei together form a network that regulates social behavior (Newman, 1999). While the regulation of social behavior is complex and involves a number of regions of the brain, two regions of the brain that may be particularly responsive to the effects of early social experience are the

Potential mechanisms: Neuropeptide regulation during development

While there are relatively few studies which identify the mechanism by which social interactions affect brain development, in the following section we will address some of the potential mechanisms through which early social experience could affect neuropeptide production. Changes in neuropeptide production may, in turn, alter development of the brain. We focus on neuropeptides because their release and production are linked with physical contact and social interaction, including nursing, which

Summary

This review has addressed the role of early social experience in the development and expression of social behavior through its effects on the function of the neuropeptides, OT and AVP, and steroids, with an emphasis on ERα. While genes are important regulators of social behavior, perhaps setting the boundaries of expression, the development and ultimate expression of social behavior can be strongly influenced by non-genomic/epigenetic factors. The postnatal period is a period of significant

Acknowledgements

We are grateful to our collaborators and the members of our lab for their technical assistance and their support: D. Barse, Dr C.S. Carter, N. Cushing, Dr P.M. Epperson, J. Hazelton, Dr G.E. Hoffman, Dr W.W. Le, K. Levine, J. Martin, N. Mogekwu, Dr A.Z. Murphy, U. Okorie, Dr M.A. Ottinger, E. Papademetriou, A. Perry, M. Raptos, Dr M. Razzoli, J. Wu, Dr Y. Yamamoto, Dr L.J. Young. We also thank the many students who provided animal care. This work was supported by grants from NIH MH 01992

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    Present address: Department of Biology, University of Memphis, Memphis, TN 38152, USA.

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