屏状核的发育与演化

人类大脑是长期进化的结果,也是思维意识与情感的物质承载。如此精密复杂的结构，是如何演化来的？利用单细胞转录组测序与绘制基因表达图谱相结合的方法，申请人及同事发现了负责学习记忆功能的海马，从爬行动物到哺乳动物显示出高度的进化保守性。哺乳动物海马结构中的亚区，多已存在于爬行动物脑中。这项研究将海马的起源追溯到了爬行动物和哺乳动物最后共同的祖先。但是边缘系统的屏状核，其起源尚不明确。一个原因是缺乏跨物种的基因表达和神经连接图谱数据，另一方面也缺乏屏状核发生发育的理解。为了解决该问题，申请人计划从个体发育和物种进化中寻求答案，通过1）横向比较多物种屏状核基因表达图谱；2）追踪屏状核神经元的发育和迁徙；3）利用转基因鼠系细化屏状核到皮层的投射4）研究屏状核特定神经元在睡眠觉醒中的作用等实验，建立跨物种屏状核演化和发育的模型，为深入理解屏状核的结合和功能提供数据和理论。

The human cerebral cortex arguably the most complex structure created by evolution but how it evolved from its reptile-like and early mammalian ancestors remains a mystery. Some parts of the cortex are greatly enlarged in humans, such as the neocortex, while other parts such as the olfactory cortex are relatively small. Surrounding the neocortex are the regions of the cortical limbic system that mediate awareness, internal sensations, and memory. The limbic system consists regions with a layered neuronal structure such as the hippocampus and other regions that appear to be cortical nuclei, like the claustrum. Using gene expression patterns, we have shown conclusively that some parts of the limbic system such as the hippocampus are highly conserved from reptiles to mammals. This is likely also true for the claustrum, although proposals about the location of the claustrum homolog in reptiles vary. However, the deeper origin of the claustrum and the evolutionary diversification of claustrum specific cell types remains largely unknown, making it difficult to draw inferences across species, primarily due to a lack of critical connectivity gene expression data from reptiles, rodents, and primates. For example, the claustrum in rodents is largely intermingled within other regions of the cerebral cortex, while in primates the claustrum is a nucleus separated from cortex by a barrier of white matter. Studies on gene expression in the developing claustrum have the potential to clarify the relationships and identity of the claustrum proper and the location of all claustrum cell types in adult animals. The cells of the claustrum primordium express the nuclear receptor Nurr1; they are formed in in the anterior-lateral parts of the cerebral hemisphere at the site of the future insular cortex. While the majority of cortical neurons are generated in an inside-out pattern and do not move very far from their origin via tangential migration, very little is known about the potential of claustrum neurons to migrate through the developing cortex, which may contribute to the observed widespread distribution of claustrum specific markers throughout the cortex. Here we propose to contribute to a novel understanding of claustrum evolution and development (evo-devo) by (i) matching anatomical gene expression patterns and connection data from reptiles to rodents and primates,(ii) fate-mapping studies of claustrum neurons in the developing cerebral cortex, (iii) use newly generated transgenic lines with specific expression patterns in entorhinal cortex and insular cortex for refined cell-type and circuit identification, (iv) investigating the functional role of distinct classes of claustrum neuron subtypes in sleep regulation and attention, (v) develop a new model of cortical evolution that emphasizes and explains the emergence of complex limbic system regions such as entorhinal cortex and insular cortex.