The Developmental Origins of Cerebral Cortical Expansion in Evolution & Disorder

描述（由申请人提供）：本提案的目的之一是确定进化如何改变发育，使灵长类动物与其他哺乳动物（如啮齿动物）相比，具有扩大的大脑皮层和减少的边缘系统（如嗅球、隔膜、杏仁核）。先前的研究表明，与啮齿类动物相比，灵长类动物的皮层神经发生是延迟的，而边缘系统的神经发生是提前的。然而，这些发现并不能排除神经发生发生之前的事件可以解释不同物种的皮层和边缘系统在成年时大小变化的可能性。灵长类动物大脑皮层的扩大和边缘系统的缩小可能在神经发生开始之前就出现了。具体来说，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。本研究的另一个主要目的是利用结构磁共振成像技术来研究成年人类大脑区域大小的变化。与进化稳定的结构相比，物种间变异性增加的结构在同一物种内也可能更具变异性。个体差异可能带来好处（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层可能表明了自然范围的极端。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. PUBLIC HEALTH RELEVANCE: Autism is associated with an enlargement of the cerebral cortex and reduction of some limbic structures. These developmental alterations might arise because of alterations in brain patterning or developmental timing but we currently understand very little about these neurological defects. Understanding how brains change in evolution will help elucidate how brains change mal-adaptively.