UNDERSTANDING NEURODEVELOPMENT IN MACAQUES WITH DIFFERENT REARING EXPERIENCES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们使用了一个自然主义的非人类灵长类动物早期生活应激(ELS)模型，包括糟糕的母体护理，利用体内神经成像技术，使用结构MRI、弥散张量成像(DTI)和磁共振波谱来表征ELS对神经发育的长期影响。 为了了解对大脑发育的影响，我们必须检查恒河猴幼年时期正常的大脑发育，并分析与社会情绪成熟的潜在联系。我们的发现揭示了婴儿时期大脑发育的戏剧性变化，特别是在2周至3个月之间，包括脑体积增加，脑沟加深和强烈的髓鞘形成速度。我们发现，在2周时，一些皮质区域，如前额叶皮质，还没有髓鞘。这些发现突显了大脑，特别是长期发育的前额叶回路，在这些早期经历的压力下高度脆弱，这可能导致正常大脑发育轨迹的改变。 我们使用一个糟糕的产妇护理模型来证明ELS确实影响大脑发育。例如，在青春期检测到脑髓鞘束的长期变化，特别是在前额叶、颞叶、顶叶和视觉皮质。我们发现，患有ELS的动物的杏仁核体积显著减少，尽管总体大脑、灰质或白质体积没有差异，或者其他感兴趣的区域(如海马体)没有差异。有趣的是，杏仁核体积与基础皮质醇在1个月时呈负相关，当时动物在婴儿时期经历了最高水平的应激。 总之，我们的发现表明ELS对非人类灵长类动物边缘脑区的结构和连通性有长期影响。在青春期检测到的杏仁核体积缩小似乎与生命早期应激诱导的皮质醇升高有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We used a naturalistic nonhuman primate model of early life stress (ELS) consisting of poor maternal care to characterize the long-term impact on neurodevelopment using in vivo neuroimaging technology, using structural MRI, diffusion tensor imaging (DTI) and MR spectroscopy. In order to understand the effects on brain development, we had to examine normative brain development during the rhesus monkey infant period, and analyzed potential associations with socioemotional maturation. Our findings revealed dramatic brain developmental changes during infancy, particularly fast and striking between 2 weeks and 3 months, including increased brain volume, deepening of sulci and intense rates of myelination. We found that at 2 weeks some cortical regions, such as the prefrontal cortex, were not yet myelinated. These findings underscored the high vulnerability of the brain, particularly prefrontal circuits with protracted development, to stress experienced at these early ages, which could result in alterations in normal brain developmental trajectories. We demonstrated that ELS indeed affects brain development using a model of poor maternal care. For example, long-term alterations in brain myelinated tracts were detected during adolescence, particularly in prefrontal, temporal, parietal and visual cortices. We found a significant decrease in amygdala volume of animals with ELS, despite no differences in overall brain, gray or white matter volumes, or in other regions of interest (e.g. hippocampus). Interestingly, the amygdala volume negatively correlated with basal cortisol at month 1, when animals experienced the highest levels of stress as infants. Altogether, our findings suggest the ELS has long-term effects on the structure and connectivity of limbic brain regions of nonhuman primates. The reduced amygdala volume detected during the adolescent period seems related to the stress-induced elevations in cortisol early in life.