Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene–environment interactions?

Abstract

This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that are determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms.

Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: role of social experience and adaptive coping behavior

“…Adolescence is considered a period of hypersensitivity to stressful events as illustrated by slower return to baseline of stress-stimulated plasma corticosterone compared to adults (Goldman et al 1973; Romeo 2010). Adolescent-typical social behaviors, such as play fighting, are essential for the development of normal adult social behaviors (Hall and Perona 2012; Lukkes et al 2009c). The long-term effects of adolescent social deprivation and adolescent social defeat overlap because both sensitize the mesocorticolimbic dopamine system (Burke et al 2010; Whitaker et al 2013) and increase measures of psychostimulant reward (Burke et al 2011; Howes et al 2000).…”

Enduring effects of post-weaning rearing condition on depressive- and anxiety-like behaviors and motor activity in male rats

“…Particular experiences, often at particular critical periods during development, produce permanent alterations in behavior [14]. The simplest way to manipulate experience is to compare the animals placed in different environments [18].…”

Long-Term Functional Outcomes and Correlation with Regional Brain Connectivity by MRI Diffusion Tractography Metrics in a Near-Term Rabbit Model of Intrauterine Growth Restriction

“…Evaluation of the long-term effects of IUGR on the human brain is limited by the difficulty of conducting prospective studies in sufficiently large sample sizes, and the potential influence of uncontrolled environmental factors [41]. Notwithstanding the obvious limitations, animal models provide the opportunity to conduct comprehensive studies spanning long maturational periods in homogeneous groups.…”