Using evolutionary variation to probe the neural basis for behavior

动物的行为表现出惊人的多样性，但几乎没有人知道进化是如何进行的。 神经回路的变化引起了物种特异性行为的变化。在这里我提议利用 基因组编辑的最新进展，并开发一种创新方法来揭示进化如何塑造 大脑回路使用CRISPR基因组编辑技术，我们正在将神经遗传学工具从D. 黑腹果蝇到其他果蝇物种，允许第一个高分辨率的解剖和功能神经 跨物种的电路映射。通过直接比较同源的感觉加工通路， 相关的果蝇，我们将精确地指出适应性变化发生在神经系统内， 系统来产生特定物种的交配偏好。果蝇求偶的快速进化使我们能够 系统地探讨如何在行为上的平行变化已经独立地实施在不同的 物种，揭示了大脑回路中允许和优选的变化类型。 绘制这些通路中解剖和功能变化的位点将进一步使我们能够研究它们的 潜在的分子基础，使用相关神经群体的转录谱， 基因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，细胞和电路水平的变化 跨越物种。由于许多大脑疾病的病因是异常的神经回路布线， 对基因、神经回路和行为之间联系的理解可能会对人类产生深远的影响。 心理健康

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.