The Developmental Origins of Cerebral Cortical Expansion in Evolution & Disorder

描述(申请人提供)：本提案的一个目的是确定与其他哺乳动物(例如啮齿动物)相比，进化如何改变发育，使灵长类拥有扩大的大脑皮层和减少的边缘系统(例如嗅球、隔膜、杏仁核)。先前的研究表明，与啮齿动物相比，灵长类动物皮质神经发生的时间较长，而边缘系统的神经发生较早。然而，这些发现并不排除神经发生开始之前的事件解释成人大脑皮质和边缘系统大小不同物种的可能性。灵长类动物大脑皮质的扩张和边缘系统的缩小可能会在神经发生开始之前出现。具体地说，我将测试灵长类动物大脑皮层的扩张是否是由于大脑模式和/或细胞周期动力学的变化。这项提议的另一个主要目的是使用结构磁共振成像来检查人类成年后大脑区域大小的变化。与进化上稳定的结构相比，物种间变异性增加的结构在物种内也可能更具变异性。个体变化可能会带来收益(例如，适应性变化)和成本。例如，在自闭症患者身上发现的异常大的额叶皮质可能预示着自然范围的极端。了解灵长类动物大脑扩张及其自然变异的发育机制，将增强我们对发育中适应性和非适应性变化的基本原理的理解。

DESCRIPTION (provided by applicant): One aim of the present proposal is to determine how evolution altered development to endow primates with an expanded cerebral cortex and a reduced limbic system (e.g., the olfactory bulb, septum, amygdala) compared with other mammals (e.g. rodents). Previous work has shown that cortical neurogenesis is protracted whereas neurogenesis in the limbic system is advanced in primates compared with rodents. However, these findings do not preclude the possibility that events prior to neurogenesis onset account for adult variations in the size of the cortex and limbic system across species. The expanded cerebral cortex and reduced limbic system of primates might emerge before neurogenesis begins. Specifically, I will test whether the expansion of the cerebral cortex in primates is due to changes in brain patterning and/or cell cycle kinetics. Another major aim of the present proposal is to use structural magnetic resonance imaging to examine the variation in brain region size of humans in adulthood. Compared with evolutionarily stable structures, structures with increased variability between species may also be more variable within a species. Individual variation likely comes with benefits (e.g., adaptive changes) as well as costs. For example, the abnormally large frontal cortex found in patients with autism may be indicative of an extreme end of a natural range. Understanding the developmental mechanisms that underlie the expansion of the brain in primates and its natural variation will enhance our understanding of the basic principles underlying adaptive and mal-adaptive changes in development.