ReviewEpigenetics and its implications for behavioral neuroendocrinology
Introduction
The early stages of life, beginning before birth and, in mammals up to weaning, are the time of maximal neuronal plasticity. Although the individual’s capacity to respond to environmental change or insult with heritable phenotypic variation at a later stage is possible, it is during this early period that hormones and genotype predispose an individual’s responses to future experiences throughout the life cycle as well as the susceptibility to developing disorders (e.g., [8], [9], [32], [38], [48], [59]). Obviously, suites of genes underlie the fundamental plasticity of an organism, particularly during development or life history transitions. How do these gene networks interact with the experiences that cumulate during an individual’s life history?
An important interface between the environment (either internal or external) and the genotype is that of epigenetic modifications (Fig. 1). Exactly how these modifications come about is still relatively unknown, but recent studies at both the molecular and organismal levels indicate that the origin of such effects may occur in previous generations. That is, experiences of earlier generations can modify regulatory factors affecting gene expression such that the DNA sequence itself is not changed but the individual’s physiology and behavior are substantially influenced not only as an effector but also as an affector system. And, as depicted in Fig. 1, further dimensions also apply in the form of both animal and human culture inheritance systems [57]. In a real sense, it may be said that Lamarck was right; he was simply born in the wrong century [57], [83]. Thus, understanding how such modifications actually occur will increase our understanding of how the environment influences the relationship between genotype and behavior during sensitive developmental periods. Before reviewing this literature, it is important to first point out the dual origins of the study of epigenetic modification or what I term Molecular versus Molar epigenetics and, secondly, to distinguish between mitotic (non-germline) versus meiotic (germline) epigenetic imprints, or what I term Context-Dependent versus Germline-Dependent epigenetic modifications.
Section snippets
Molecular versus Molar epigenetics
There have been several reviews recently as to the origins of the field of epigenetics, all of which recognize the multiple roots of the current tree of research (e.g., [11], [48], [52], [53], [107], [56]). Unfortunately, almost all have been written by molecular and developmental biologists who, being genocentric, are not versed in the history of the psychological or behavioral sciences (for exceptions, see [43], [44], [57]).
The debates in the natural sciences in the 16th–17th centuries pitted
Context-Dependent versus Germline-Dependent epigenetic modifications
It is commonly thought that epigenetic modifications that occur within an individual’s own lifetime have the ability to become inherited. But unless one considers, for example, the cultural transmission of royalty an epigenetically modified state, this is not so. (That is, speaking of royalty in humans and not in honeybees [86]). At a molecular level, CpG sites however are often associated with 5′ promoter regions of genes and have a higher probability of undergoing mutation than other regions
Epigenetics, behavior and the brain
If the context in which the individual is nurtured influences its behavior as an adult, it is likely that the activity of the neural circuitry that underlies these behaviors must also be affected. This organizational principal should also apply to epigenetic modifications whether within the individual’s own life history (Context-Dependent) or inherited from previous generations (Germline-Dependent) (see articles [16], [39]). What follows are two case studies, the first demonstrating how the
Conclusion
The future for epigenetic studies in neuroendocrinology is going to depend upon communication, principally between those schooled in what might be called collectively psychobiology (comparative and physiological psychology, behavioral neuroendocrinology, and behavioral biology) and molecular and developmental biology. Typically, scientific progress is in fits and starts, advancing only when practitioners in one discipline become aware of, and appreciate, other fields working on common problems
Acknowledgments
The work reported herein was supported in part by grants from the NIMH (R21 MH068273 and ROl MH41770). I thank Gwen Cage for the illustration in Fig. 1, Vicky Huang for assistance with Fig. 4, Fig. 5, Michael Skinner for permission in using a component of Fig. 6, and P. Bateson, G. Galef, E. Jablonka, M. McCarthy for critical comments on the manuscript.
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