Research reportDifferential rearing affects corpus callosum size and cognitive function of rhesus monkeys
Introduction
Social experience appears to be essential for normal primate behavioral development. In rhesus monkeys, social deprivation early in development is associated with profound and enduring increases in abnormal self-directed (autistic-like) behaviors, alterations in normal social behavior, deficits in exploration, communication, emotionality and sexual and maternal behaviors 33, 63. The precise behavioral consequences depend on the extent, the duration, and the age at which social deprivation occurs, but there is little question that infants are more vulnerable than adults and that isolation through the first year leads to irreversible changes in behavior [33].
Although there has been extensive research into the mechanisms by which social deprivation alters behavioral development, there have been relatively few studies of its neurobiological consequences. Indeed, we know very little about how social experience contributes to normal neural development and, as a consequence, normal cognitive function in primates. Early studies in macaques reported decreases in dendritic branching in cortical stellate cells [62]and cerebellar Purkinje cells [22], but these changes likely result from rearing in conditions of low environmental complexity rather than a specific loss of social interaction. Other groups have described neurochemical changes subsequent to early social deprivation, such as decreases in dopamine innervation of the neocortex and striatum, but not in other structures, such as the amygdala [47]. These results, however, are confounded by aging effects which might have contributed to group differences. More recent studies that have compared juvenile monkeys (19–27 months) raised in isolation or social housing have found no differences in dopaminergic or noradrenergic innervation of the hypothalamus, or in corticotropin releasing hormone content in the hypothalamic paraventricular nucleus 26, 27.
To our knowledge, there has been no previous investigation of how social experience contributes to primate brain development using structural brain imaging. Several studies in rodents have described changes in neuronal morphology based on environmental enrichment 1, 15, 18, 31, 41, 64and clinical studies using MRI have described decreased hippocampal volume in adult post-traumatic stress disorder patients with a history of childhood abuse 10, 61. The current study used high resolution MRI to investigate differences in neural development associated with differential rearing of rhesus monkeys (Macaca mulatta). In addition, subsets of these animals were assessed for specific cognitive functions, such as visual recognition memory, visual formation habit, and executive function by means of the delayed non-matching to sample (DNMS), simple object discrimination and object/spatial reversal learning tasks, respectively.
Section snippets
Animals
The experimental animals were obtained from a population of macaque infants originally reared for immunologic studies. These studies required nursery-rearing of the infants from the 7th until the 48th week of age (NURSERY, n=9). Nursery-reared monkeys were housed in individual cages in rooms with automatically regulated temperature and lighting conditions (light/dark, 0600 h/1800 h). These animals could, at any time, see and hear other animals in the colony, and had physical contact with
General observations
As expected from previous descriptions 33, 63, NURSERY animals exhibited a syndrome of abnormal behaviors, including increased locomotor activity, as well as stereotypic, self-injurious, self-oral, or clinging behaviors not shown by the CONTROL infants. They also showed reduced social contact in comparison to CONTROL animals [57]. One of the animals in the CONTROL group had to be released from the study due to chronic illness following his transfer from the Field Station social group to the
Discussion
NURSERY animals showed a decrease in CC midsagittal area (especially in its caudal aspects) accompanied by a decrease in white (but not gray) matter volume in parietal and prefrontal cortex. Nursery-rearing had no detectable effects on brain, cerebellar, hippocampal or prefrontal cortex volumes, or on the size of the AC. The alterations found in CC size persisted despite introduction of the NURSERY animals into a peer-group for 6 months. In relation to cognitive function, the NURSERY macaques
Acknowledgements
This work was supported by the Yerkes Regional Primate Research Center base grant No. RR-00165 awarded by the Comparative Medicine Program, National Center for Research Resources of the National Institutes of Health. Support was also provided by NIH grant PO1-AG0001. The authors thank Dr. R. Nisenbaum for statistical advice, and gratefully acknowledge Dr. T.R. Insel's help during this study and his critical review of the manuscript.
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