Nonhuman primate models of hippocampal development and dysfunction

Abstract

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 hypothalamic–pituitary–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.

Clinical and Preclinical Evidence for Adverse Neurodevelopment after Postnatal Zika Virus Infection

“…Memory impairment suggests that postnatal ZIKV infection affects the development of the brain areas that are important for visual learning and memory function. The lack of observed impairment at the earlier age we evaluated is reflective of the studies demonstrating that early hippocampal insults result in cognitive impairments that emerge later in development [ 96 , 97 ], meaning that longer clinical follow up may be required in order to detect the impact of postnatal ZIKV infection on learning and memory function.…”

Contributions of nonhuman primate research to understanding the consequences of human brain injury during development

“…49-51) documenting that, in adults, the declarative and procedural memory systems compete for cognitive control. Bachevalier's work (44,52) extends these findings to the developmental period.…”

“…Work on NHP models has been instrumental in defining how the declarative memory system may respond to early insult. Bachevalier (44) and others (45) have made extensive use of developmental lesion studies, coupled with careful neuropsychological assessments, to define the time course of emergence of hippocampaldependent cognitive functions and the effects of early insult on their subsequent maturation.…”

“…The team led by Bachevalier (44) reports that neonatal hippocampal lesions result in facilitation of object discrimination (tested via paired and concurrent object discrimination tasks), a cognitive function thought to rely on the procedural memory system. There is a large literature (e.g., refs.…”

COVID-19—The largest isolation study in history: the value of shared learnings from spaceflight analogs

“…THE DLPFC and the OFC are pivotal for executive control such as response inhibition, working memory and cognitive flexibility 36 , but also the generation of and regulation of emotion 37 . Projections between the hippocampus and orbitofrontal cortex (OFC), and to some extent also the DLPFC 38 , can foster cross-structural communication, and might interact to influence behavior 39 . Data from the ICC analog NEK also suggest decreases in white matter integrity of the right temporoparietal junction (TPJ) after prolonged isolation and confinement 40 .…”