Nonhuman primate models of hippocampal development and dysfunction

Nonhuman primates provide highly valuable animal models that have significantly advanced our understanding of numerous behavioral and biological phenomena in humans. Here, we reviewed a series of developmental neuropsychological studies that informed us on the timing of development of the hippocampus and of hippocampal-dependent cognitive functions in primates. Data indicate that, in primates, the emergence of adult-like proficiency on behavioral tasks sensitive to hippocampal dysfunction is a stepwise process and reflects the gradual maturation of different hippocampal circuits and their connections with other neural structures. Profound and persistent memory loss resulting from insult to the hippocampus in infancy was absent in early infancy but became evident later in childhood and persisted in adulthood, indicating very little sparing or recovery of function. Finally, the early hippocampal insult resulted in both adaptive and maladaptive neuroplasticity: i.e., sparing contextual memory, but affecting working memory processes as well as emotional reactivity and hypothalamicpituitary-adrenal (HPA) axis functioning. The results provide significant information on the emergence of hippocampal-dependent functions in humans, on the time course of memory impairment in human cases with early hippocampal insult, and on the clinical implication of the hippocampus in developmental neuropsychiatric disorders.