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

行为研究的一个核心挑战是理解基因变化导致行为变化的机制。虽然筑巢是一种可遗传的、可控制的行为，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和控制这种行为的精确神经回路是未知的。该研究项目将补充正在进行的遗传研究，并通过识别在筑巢期间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。这些是理解遗传变化如何改变哺乳动物神经系统结构和功能的关键步骤，这是一个超越筑巢行为的探索领域。此外，这是一个独特的机会，可以确定在自然进化的种群中导致行为差异的基因变化，这种例子非常罕见，特别是在哺乳动物中。由于这种基因变异正在野生啮齿动物种群中分离，这些实验的结果将为哺乳动物行为的进化提供见解，这可能广泛适用于包括人类在内的其他物种。最后，研究人员将制作视频和教育材料，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、哈佛大学比较动物学博物馆教师资源页面和国家生物教师协会免费提供给教育工作者和公众。该项目重点研究了两种姊妹物种脊髓灰质炎大鼠（Peromyscus polionotus）和鹿鼠（P. maniculatus），它们在建立具有体温调节价值的巢穴方面的潜伏期不同，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，并最终改变对健康重要的行为。两个物种之间的交叉培养实验证明了这种差异是可遗传的，定量性状位点（QTL）定位实验确定了3个基因组区域有助于种间变异，其中一个位点仅包含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期间大脑中活跃的细胞群，这本身就是一个新发现，并且将允许后续实验关注与行为差异最相关的大脑区域和细胞。在此之后，研究人员将使用先进的磷酸化核糖体分析技术来表征那些在筑巢期间特别活跃的神经元的转录组。总之，这些目标将缩小由遗传作图方法产生的候选基因列表，并提供对这些基因变化如何改变神经回路以产生行为差异的见解。研究人员还将使用VideoScribe （http://www.videoscribe.co/）制作适合高中/本科生观众的简短教育视频，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.