Genomic Bases of Evolution of Homologous Neurons & Neuronal Circuits

同源神经元进化的基因组基础

• 批准号: 0744649
• 负责人: Leonid Moroz
• 金额: $ 26万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0744649&HistoricalAwards=false
• 关键词: Genomic; Bases; Evolution; Homologous; Neurons

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.

这项研究将阐明神经元电路进化的最具挑战性的方面之一：基因组机制，基因组机制特异性的适应性修饰和新型行为的起源。 在现代神经科学中，进化方法的发展较少。 但是，了解如何形成复杂的网络和大脑或回答“为什么”问题至关重要（例如为什么在不同的神经元电路中选择了不同的信号分子子集）。 集中式复合大脑的演变并行发生，在不同的谱系中可能独立出现独立的神经模式，但使用相似的分子构建块或工具包。该项目提议识别和表征整个Opisthobranch物种（例如Pleurobranchaea和Tritonia）中定义的神经电路中的细胞同源物，以了解同源神经元基因组组织的变化如何导致网络逃生和其他行为的自适应修饰。 结果，当可以通过单细胞分辨率以整个基因组量表描绘神经系统进化时，这将导致概念上的新方法。 关于神经回路的发散演变是否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被测试。 另外，新型的网络特性和连接可能会作为先前存在的分子组件的模块化重排。 在开发全国性比较基因组数据库期间，将出现跨学科学生的培训机会，该数据库将可以搜索神经元标记和信号转导途径。 成绩单的广泛收集还将允许在神经生物学模型的神经生物学模型中测试进化关系，其神经系统的集中度不同。 拟议的方法和方法可以推广到任何系统，因此将大大增加从研究经典电生理准备中获得的信息和教育机会。 该研究将提供神经科学和比较基因组学的长期婚姻，以了解特定的神经元网络的组织和发展。