Neural and genetic basis of social behavior in cichlid fish

项目概要： 这项研究的总体目标是调查神经和遗传基础， 攻击性行为的自然差异攻击性有很强的遗传性 然而，我们对基因组中的变异如何改变大脑知之甚少。 功能来改变行为。我们所知道的关于 遗传变异和社会行为来自少数传统的实验室模型 有机体使用一种新的自然脊椎动物系统，我们采用跨学科的方法， 研究遗传多态性在产生神经和行为变异中的作用。摇滚- 东非马拉维湖的沙栖慈鲷鱼是密切相关的， 基因组非常相似，但它们在社会行为方面表现出很大的多样性，包括 侵略在目标1中，我将量化岩石和沙子之间攻击行为的差异- 栖息物种和它们的杂交种在目标2中，我将首先绘制在大脑中被招募的区域， 通过可视化神经活动标记的表达来控制攻击。第二，我会 通过对攻击激活神经元的基因表达模式进行测序， 转录组，使我们能够发现新的遗传变异与差异， 行为通过比较不同物种及其杂交种的结果，我们将深入了解 神经和基因组机制潜在的表型变异的侵略。在目标3中， 将测试加压素中的候选基因变体对大脑和行为的影响 通过CRISPR-Cas9基因组编辑技术获得激素受体基因。这种综合方法 旨在提供洞察攻击性的变化如何通过微小的变化产生 基因的序列或调控。总之，这种策略将确定神经系统如何 调节基本社会行为的回路在远系繁殖的动物中被控制在基因组水平上， 脊椎动物，提供了人类行为多样性的模型。

PROJECT SUMMARY: The overarching goal of the proposed research is to investigate the neural and genetic basis of a naturally-occurring difference in aggressive behavior. Aggression has a strong genetic component, and yet we understand very little about how variation in the genome alters brain function to produce changes in behavior. Most of what is known about the relationship between genetic variants and social behavior comes from a small number of traditional lab model organisms. Using a novel natural vertebrate system, we employ an interdisciplinary approach to investigate the role of genetic polymorphisms in producing neural and behavioral variation. Rock- and sand-dwelling cichlid fishes from Lake Malawi in East Africa are closely-related and their genomes are very similar, yet they exhibit substantial diversity in social behaviors, including aggression. In Aim 1, I will quantify differences in aggressive behavior between rock- and sand- dwelling species and their hybrids. In Aim 2, I will first map the brain regions recruited during aggression by visualizing the expression of a marker of neural activity. Secondly, I will characterize the gene expression patterns of aggression-activated neurons by sequencing their transcriptomes, allowing us to discover novel genetic variants associated with differences in behavior. By comparing these results across species and their hybrids, we will provide insight into the neural and genomic mechanisms underlying phenotypic variation in aggression. In Aim 3, we will causally test the effect on brain and behavior of a candidate genetic variant in a vasopressin hormone receptor gene via CRISPR-Cas9 genome editing technology. This integrative approach is designed to provide insight into how variation in aggression can be produced by small changes to the sequence or regulation of genes. Taken together, this strategy will identify how the neural circuits regulating an essential social behavior are controlled at the level of the genome in outbred vertebrates, providing a model of behavioral diversity in humans.