Genomic Bases of Evolution of Homologous Neurons & Neuronal Circuits

这项研究将阐明神经元电路进化中最具挑战性的方面之一：细胞特异性适应性修饰的基因组机制和新行为的起源。进化论方法在现代神经科学中发展较慢。然而，理解复杂的网络和大脑是如何形成的或回答“为什么”的问题(例如，为什么在不同的神经元回路中选择不同的信号分子子集)是至关重要的。集中化的复杂大脑的进化是平行的，不同的神经模式可能独立出现在不同的谱系中，但使用相似的分子构建块或工具包。该项目建议在不同物种(例如侧耳侧耳和侧耳侧耳)的已定义神经回路中识别和表征细胞同源基因，以了解同源神经元基因组组织的变化如何导致逃避和其他行为背后的网络的适应性修改。因此，当神经系统进化可以用单细胞分辨率在整个基因组范围内描绘时，它将导致概念上的新方法。关于神经回路的不同进化是否会导致新的信号系统和其他神经元特异性标记的出现的假设将得到测试。或者，新的网络属性和连接可能作为先前存在的分子组分的模块重排而出现。在开发全国范围的比较基因组数据库期间，将为跨学科学生提供培训机会，该数据库将可用于搜索神经元标记和信号转导途径。广泛的抄本收集还将允许测试神经系统集中程度不同的神经生物学模型之间的进化关系。所提出的途径和方法可以推广到任何系统，因此将极大地增加从研究经典电生理准备中获得的信息和教育机会。这项研究将提供人们期待已久的神经科学和比较基因组学的结合，以了解特定的神经元网络是如何组织和进化的。

This research will illuminate one of the most challenging aspects of the evolution of neuronal circuits: genomic mechanisms underlying cell-specific adaptive modifications and the origin of novel behaviors. The evolutionary approach is less developed in modern neuroscience. However, it is crucial to understand how complex networks and brains are formed or to answer "why" questions (e.g. why different subsets of signal molecules were selected in distinct neuronal circuits). The evolution of centralized complex brains occurs in parallel, where distinct neural patterning might emerge independently in different lineages but use similar molecular building blocks or toolkits. This project proposes to identify and characterize cellular homologs within defined neural circuitries across opisthobranch species (e.g. Pleurobranchaea and Tritonia) to understand how changes in the genomic organization of homologous neurons lead to adaptive modifications of networks underlying escape and other behaviors. As a result, it will lead to conceptually new approaches when nervous system evolution can be portrayed on an entire genomic scale with single-cell resolution. The hypothesis about whether divergent evolution of neural circuits resulted in the appearance of novel signaling systems and other neuron-specific markers will be tested. Alternatively, novel network properties and connections might emerge as modular rearrangements of preexisting molecular components. Training opportunities for interdisciplinary students will arise during the development of a nation-wide comparative genomic database that will be searchable for neuronal markers and signal transduction pathways. The extensive collection of transcripts will also allow testing evolutionary relationships across neurobiological models with different levels of centralization of their nervous systems. The proposed approaches and methodologies can be generalized to any system and thus will dramatically increase both the information and education opportunities that can be gained from studying classical electrophysiological preparations. The research will provide a long desired marriage of neuroscience and comparative genomics to understand of how specific neuronal networks are organized and evolved.