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Dissertation Research: The genetic and neurobiological basis of nesting behavior in two species of Peromyscus

论文研究：两种白鼠筑巢行为的遗传和神经生物学基础

基本信息

批准号：
1701805
负责人：
Hopi Hoekstra
金额：
$ 2.19万
依托单位：
Harvard University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1701805&HistoricalAwards=false
关键词：
Dissertation Research genetic neurobiological basis

项目摘要

A central challenge in the study of behavior is to understand the mechanisms by which genetic changes can cause behaviors to vary. Though nesting is a heritable, tractable behavior with profound consequences for survival and reproduction in rodents, the genes that influence this trait and the precise neural circuitry governing this behavior are unknown. This research project will complement an ongoing genetic study and bridge the gap between our understanding of genetic, neurobiological and behavioral variation by identifying the neurons that are active during nesting and characterizing gene expression patterns in these cells. These are crucial steps in understanding how genetic changes can alter the structure and function of a mammalian nervous system, an area of inquiry with implications beyond nesting behavior. Moreover, this is a unique opportunity to identify a genetic change that contributes to a behavioral difference in naturally evolving populations, examples of which are very rare, especially in mammals. As this genetic variant is segregating in wild rodent populations, the results of these experiments will provide insights into the evolution of mammalian behavior that may be broadly applicable to other species, including humans. Finally, of the researchers will create videos and educational materials including activities, problems sets, and exam questions to complement the videos that will be made freely available to educators and the public through the Hoekstra Laboratory website, the Harvard Museum of Comparative Zoology Teacher Resource Page, and the National Association for Biology Teachers.This project focuses on two sister species Peromyscus polionotus (the oldfield mouse) and P. maniculatus (the deer mouse) that differ in their latency to build nests of thermoregulatory value to further understand how genetic changes can alter the structure and function of a mammalian nervous system and, ultimately, behaviors important for fitness. Cross-fostering experiments between the two species demonstrated that this difference is heritable, and a Quantitative Trait Locus (QTL) mapping experiment identified 3 genomic regions that contribute to interspecific variation, including one locus containing only 62 candidate genes. This research will significantly extend and improve upon this existing body of work. First, the researchers will use Immediate-Early Gene (IEG) expression patterns to identify the cell populations in the brain active during nesting, which will itself be a novel finding and will additionally allow subsequent experiments to focus on the brain regions and cells most relevant for the behavioral difference. Following this the researchers will characterize the transcriptomes of those neurons specifically active during nesting using a cutting-edge phosphorylated ribosome profiling technique. Together, these aims will both narrow the list of candidate genes generated by the genetic mapping approach and provide insights into how those genetic changes modify neural circuits to produce behavioral differences. The researchers will also make short educational videos tailored to a high school/undergraduate audience using VideoScribe (http://www.videoscribe.co/) to explain basic concepts in genetics and neuroscience and their application to the study of behavioral evolution.

行为研究的一个核心挑战是了解遗传变化导致行为变化的机制。虽然筑巢是一种可遗传的、易于控制的行为，对啮齿动物的生存和繁殖有着深远的影响，但影响这种特征的基因以及控制这种行为的精确神经回路尚不清楚。该研究项目将补充正在进行的遗传研究，并通过识别在嵌套期间活跃的神经元并表征这些细胞中的基因表达模式，弥合我们对遗传，神经生物学和行为变异的理解之间的差距。这些是理解遗传变化如何改变哺乳动物神经系统的结构和功能的关键步骤，这是一个研究领域，其影响超出了筑巢行为。此外，这是一个独特的机会，以确定一个遗传变化，有助于行为差异的自然演变的人口，其中的例子是非常罕见的，特别是在哺乳动物。由于这种遗传变异在野生啮齿动物种群中分离，这些实验的结果将提供对哺乳动物行为进化的见解，这些行为可能广泛适用于其他物种，包括人类。最后，研究人员将创建视频和教育材料，包括活动，问题集和考试问题，以补充视频，这些视频将通过Hoekstra实验室网站，哈佛比较动物学博物馆教师资源页面，和全国生物教师协会。该项目的重点是两个姐妹物种Peromyscuspolionotus（oldfield小鼠）和P. maniculatus（鹿小鼠）在建造具有温度调节价值的巢穴的潜伏期方面存在差异，以进一步了解遗传变化如何改变哺乳动物神经系统的结构和功能，并最终改变对健康至关重要的行为。两个物种之间的交叉培养实验表明，这种差异是遗传的，和数量性状基因座（QTL）定位实验确定了3个基因组区域，有助于种间变异，包括一个位点只包含62个候选基因。这项研究将大大扩展和改进现有的工作。首先，研究人员将使用即时早期基因（IEG）表达模式来识别在筑巢过程中活跃的大脑细胞群，这本身就是一个新的发现，并且还将允许后续实验专注于与行为差异最相关的大脑区域和细胞。在此之后，研究人员将使用尖端的磷酸化核糖体分析技术来表征这些神经元在嵌套过程中特别活跃的转录组。总之，这些目标将缩小遗传图谱方法产生的候选基因列表，并深入了解这些遗传变化如何修改神经回路以产生行为差异。研究人员还将使用VideoScribe（http：//www.videoscribe.co/）为高中/本科生观众制作简短的教育视频，以解释遗传学和神经科学的基本概念及其在行为进化研究中的应用。