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

行为研究中的一个中心挑战是理解基因变化导致行为变化的机制。尽管筑巢是一种可遗传的、可驯化的行为，对啮齿动物的生存和繁殖有深远的影响，但影响这一特征的基因和控制这一行为的精确神经回路尚不清楚。这项研究项目将补充正在进行的遗传学研究，并通过识别在筑巢过程中活跃的神经元和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。这些都是理解基因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，这一领域的研究涉及的不仅仅是筑巢行为。此外，这是一个独特的机会，可以确定导致自然进化种群行为差异的基因变化，这种情况非常罕见，特别是在哺乳动物中。由于这种基因变异在野生啮齿动物种群中是隔离的，这些实验的结果将为哺乳动物行为的进化提供洞察，这些行为可能广泛适用于其他物种，包括人类。最后，研究人员将制作视频和教育材料，包括活动、习题集和考题，以补充视频，这些视频将通过Hoekstra实验室网站、哈佛比较动物学教师资源页面和国家生物学教师协会免费提供给教育工作者和公众。该项目关注两个姐妹物种小儿麻痹症(Oldfield小鼠)和人参鼠(鹿鼠)，它们的潜伏期不同，以建立具有温度调节价值的巢，以进一步了解基因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。这两个物种之间的交叉培养实验表明，这种差异是可遗传的，数量性状基因座(QTL)定位实验确定了导致种间变异的3个基因组区域，其中一个基因座仅包含62个候选基因。这项研究将在现有工作的基础上显著扩展和改进。首先，研究人员将使用即刻早期基因(IEG)表达模式来识别在筑巢过程中活跃的大脑中的细胞群体，这本身将是一个新的发现，并将另外允许后续实验关注与行为差异最相关的大脑区域和细胞。随后，研究人员将使用尖端的磷酸化核糖体图谱技术来表征那些在筑巢过程中特别活跃的神经元的转录本。总而言之，这些目标既可以缩小基因图谱方法产生的候选基因的范围，又可以让人们深入了解这些基因变化如何改变神经回路，从而产生行为差异。研究人员还将制作针对高中/本科生观众的教育短片，使用视频描述(http://www.videoscribe.co/))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。

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.