Effects of Adverse Rearing Experience on Organization of Brain and Behavior in Non-Human Primates

IntroductionPsychological development is a protracted process in humans, with brain circuits undergoing programmed maturational change well into the third decade of life (1,2). However, the early infancy period appears to be a particularly formative time for the development of many social and emotional traits (3,4). One of the most important contributors to infant socio-emotional development across a number of mammalian species is interaction with the mother (5-9). Maternal behavior can usually be identified as a small set of behaviors such as nursing, carrying, protecting, retrieving, and grooming, directed by the mother toward the infant (10). The manner in which these stimuli are administered to the infant can have long term consequences for both structural and functional maturation of brain circuits and for mental and physical health (11,12). Although there is a great deal of overlap in the types of nurturing behaviors directed toward the young across species, important differences exist as well, with more elaborate mother infant interactions apparent in highly social species such as many nonhuman primates, and more stereotyped patterns evident in animals with less elaborate social lives such as rodents. In addition one of the most important species differences in the effects of maternal care may not be in the type of maternal care administered but in the proportion of life in which maternal care is received. The period of dependency on the mother is much longer in most primates than most rodents and is even longer in humans than in other primates (13), thus the mother is likely to have a much greater impact on ultimate development of humans than any other species.Although the types of maternal behavior do not vary much within species there is often a fair amount of inter-individual variability in the degree and the style with which these nurturant maternal behaviors are expressed. The effects of these variations have been the subject of many studies within the human developmental literature (14,15). Inter-individual variation in maternal behavior has also been the basis for elegant models of neurobiological development in rodents (9). Although there has been some attention in nonhuman primate models to naturally occurring variation in maternal behavior (16), most of the studies in nonhuman primates have used more extreme and controlled manipulations of mother infant interaction imposed by the experimenter.Existing studies on the effects of maternal behavior in humans, while important, are confounded by many factors beyond experimental control such as genetics, socio-economics, and indirect social experience among others. In contrast, while rodent models are elegant and well controlled, rodents have a markedly different neurobiology, social repertoire, and developmental trajectory than primates and so these models may be missing some important effects of mother infant interaction, particularly as they relate to neocortical development or the emergence of complex and flexible social behavior. Furthermore, there is over 90% overlap in the genome of human and nonhuman primates (17), and many primates share highly similar neurobiology, social organization and patterns of development (18-24). Therefore the primate models of adverse rearing experience (ARE) offer a good intermediary between rodent and human experimental approaches, and particularly when combined with these other models, will likely provide important insights into basic principles of socio-emotional and neurobiological development that are affected by maternal care. ARE include isolate rearing, surrogate rearing, peer rearing, brief repeated separations and variable foraging demands. While these models can rightly be criticized for being overly austere and artificial, they also have many advantages. Subjects can easily be assigned randomly to different groups, developmental periods of manipulation can be tightly regulated and many other conditions (from social contact to room lighting) can be experimentally controlled. …