Using evolutionary variation to probe the neural basis for behavior

利用进化变异来探索行为的神经基础

• 批准号: 9924684
• 负责人: Vanessa Ruta
• 金额: $ 61.02万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9924684
• 关键词: Anatomy; Animals; Behavior; Behavioral; Brain; Brain Diseases; Clustered Regularly Interspaced Short Palindromic Repeats; Courtship; Drosophila genus; Etiology; Evolution; Exhibits; Gene Expression Profiling; Genes; Genetic; Health; Light; Link; Mental Health; Molecular; Nervous system structure; Neurologic; Partner in relationship; Pathway interactions; Population; Resolution; Sensory; Technology; Translating; Variant; comparative; genome editing; innovation; neural circuit; neurogenetics; novel; preference; relating to nervous system; tool

Animals exhibit astonishing diversity in their behavior, yet almost nothing is known about how evolutionary variation in neural circuits gives rise to species-specific behavioral variation. Here I propose to take advantage of recent advances in genome editing and develop an innovative approach to reveal how evolution sculpts brain circuits. Using CRISPR genome editing technology, we are translating neurogenetic tools from D. melanogaster to other Drosophila species, allowing for the first high-resolution anatomic and functional neural circuit mapping across species. By directly comparing the homologous sensory processing pathways in closely related drosophilids, we will precisely pinpoint where adaptive changes have occurred within the nervous system to produce species-specific mate preferences. The rapid evolution of Drosophila courtship allows us to systematically probe how parallel changes in behavior have been independently implemented in different species, shedding light on the types of changes that are permissible and preferable within brain circuits. Mapping the sites of anatomic and functional change within these pathways will further enable us to study their underlying molecular basis, using transcriptional profiling of the relevant neural populations to provide a definitive link between genetic and behavioral variation. Together, the proposed studies will transform our understanding of the molecular, cellular, and circuit-level changes that generate adaptive behavioral variation across species. As the etiology of many brain disorders is aberrant neural circuit wiring, a deeper understanding of the link between genes, neural circuits, and behavior could have profound consequences for mental health.

动物的行为表现出惊人的多样性，然而关于它们是如何进化的几乎一无所知 神经回路的变异会导致物种特有的行为变异。在这里，我建议利用 并开发了一种创新的方法来揭示进化是如何塑造 大脑回路。使用CRISPR基因组编辑技术，我们正在翻译D。 与其他果蝇物种相比，黑腹果蝇可以制造出第一个高分辨率解剖和功能神经 不同物种间的电路图谱。通过直接比较同源感觉加工通路的密切关系 相关的果蝇，我们将准确地定位神经内发生了适应性变化的地方 系统来产生特定物种的配偶偏好。果蝇求偶的快速进化使我们能够 系统地探索并行的行为变化是如何在不同的 物种，揭示了大脑回路中允许和最好发生的变化类型。 绘制这些通路内解剖和功能变化的位置图将进一步使我们能够研究它们 潜在的分子基础，使用相关神经群体的转录图谱来提供 基因变异和行为变异之间的明确联系。总之，拟议的研究将改变我们的 了解产生适应性行为变化的分子、细胞和电路级别的变化 跨物种。由于许多脑部疾病的病因是神经回路连接异常，更深一层 了解基因、神经回路和行为之间的联系可能会对 心理健康。