Genetics of Brain and Behavioral Modifications in Response to Social Interactions

描述(由申请者提供)：项目摘要动物有很多机会从彼此那里获取信息。虽然社会学习在不同的类群中很常见，但社会学习需要联想学习、记忆和社会行为(LMS)的整合；而且在一个物种内的不同个体之间，这些差异很大。遗传差异如何导致神经功能的改变，最终导致社会学习的可变性？要解决这个问题，重要的是要确定在LMS中起作用的基因和神经回路。在这里，我们建议分析果蝇LMS个体差异的分子遗传学基础。苍蝇被广泛用作研究发育、行为和学习的遗传基础的模型，苍蝇是聚集在一个大群体中的社会性动物。这种融合提供了一个机会来研究个体基因差异是如何导致社交和学习上的差异的。我们将开发苍蝇作为一个模型，用于对LMS的遗传、生化、生理和环境成分进行综合分析。我们假设，特定神经回路中的转录被经验修改，这有助于长期记忆。此外，我们假设，这些相同的神经回路在不同个体之间转录的差异导致了LMS的差异。在果蝇中，蘑菇体是学习和认知的神经中枢。使用一种新的分子遗传学技术，可以从细胞亚群中提纯RNA，我们将检查192个重复杂合子F1基因型的MB转录组和LMS行为的变异。这些F1个体将从192个测序的天然罗利菌株的后代中获得，每个菌株都与一个测序的w1118菌株杂交。我们将能够：i)确定LMS的转录变异如何与表型变异相关，ii)划分每个基因表达变异的顺式和反式成分，iii)专注于与行为变异相关的顺式表达变异，以及iv)精确定位可能导致顺式表达变异的顺式DNA多态。一旦我们确定了MB表达变异的原因，我们将把转录组与LMS联系起来：我们的目标是识别与LMS差异相关的候选基因及其多态。我们将用LMS候选基因中的自然和主效等位基因在几个社会背景下测量局部基因型的幼虫和成虫的行为。然后，我们将确定由于这些社交接触而导致的MB转录差异。随后对候选基因的功能分析将提供有关基因如何影响LMS的机械性知识。总而言之，我们提出了一项研究，我们合成了关于个体基因类型的遗传、分子和行为信息，以最终破译社会学习的群体遗传学的各个方面。我们相信，我们的推论将在多个水平上阐明苍蝇自然种群中维持的LMS变异范围，从而为包括人类在内的其他社会有机体中LMS变异的遗传基础提供洞察。

DESCRIPTION (provided by applicant): PROJECT SUMMARY Animals have numerous opportunities to acquire information from one another. Although common across taxa, social learning requires the integration of associative learning, memory and social behavior (LMS); and these vary considerably among individuals within a species. How do genetic differences cause alterations in neural functions that ultimately cause variability in social learning? To address this question it is important to identify the genes and neural circuits that play a role in LMS. Here we propose to analyze the molecular-genetic basis that underlies individual differences in LMS in the fruit fly Drosophila melanogaster. Flies have been used extensively as a model to study the genetic basis of development, behavior and learning and flies are social animals that aggregate in large groups. This confluence provides an opportunity to examine how individual genetic differences underlie variation in sociality and learning. We will develop flies as a model for the integrated analyses of the genetic, biochemical, physiological, and environmental components of LMS. We hypothesize that transcription in specific neural circuits is modified by experience and this contributes to long- term memory. Further, we hypothesize that variation in transcription in these same neural circuits across individuals contributes to the differences in LMS. In Drosophila, the mushroom body (MB) is the neural center of learning and cognition. Using a new molecular-genetic technique that allows for the purification of RNA from subsets of cells, we will examine the variation in both the MB transcriptome and the LMS behaviors of 192 recurrent heterozygous F1 genotypes. These F1 individuals will be obtained from progeny of 192 sequenced natural Raleigh strains, each crossed to a sequenced w1118 strain. We will be able to: i) determine how transcriptional variation in LMS is associated with phenotypic variation, ii) partition the cis- and trans- components of expression variation for every gene, iii) focus on cis- expression variation that is associated with behavioral variation, and iv) pinpoint cis- DNA polymorphisms likely contributing to cis- expression variation. Once we have identified causes of MB expression variation, we will connect the transcriptome with LMS: our goal is to identify the candidate genes and their polymorphisms associated with differences in LMS. We will measure larval and adult behaviors of focal genotypes with natural and major-effect alleles in the LMS candidate genes in several social contexts. We will then determine the transcriptional differences in the MB that are due to these social encounters. Subsequent functional analyses of candidate genes will provide mechanistic knowledge about how genes contribute to LMS. In sum, we propose an investigation where we synthesize genetic, molecular and behavioral information about individual genotypes to ultimately decipher aspects of the population genetics of social learning. We believe our inferences will illuminate, at several levels, the range of LMS variation maintained in natural populations of flies, thus providing insight into the genetic basis of LMS variation in other social organisms, including humans.