DISSERTATION RESEARCH: The genetic and neurobiological mechanisms of species-specific burrowing behavior in deer mice

论文研究：鹿鼠物种特异性挖洞行为的遗传和神经生物学机制

• 批准号: 1209753
• 负责人: Hopi Hoekstra
• 金额: $ 1.5万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1209753&HistoricalAwards=false
• 关键词: DISSERTATION; RESEARCH; genetic; neurobiological; mechanisms

The primary objective of this project is to understand the genetic and neurobiological mechanisms that give rise to natural variation in behavior. The research will focus on difference in burrowing behavior between two closely related species of North American mice (genus Peromyscus): oldfield mice consistently excavate long, multi-tunnel burrows, while a sister species, the deer mouse, builds short burrows with a single tunnel. This species-specific difference in burrow structure is heritable, and genes potentially involved in regulating in burrow architecture have been identified. This study proposes to manipulate gene expression in each species to determine how genes act in the brain to create behavioral difference leading to different burrow structures. A QTL has been isolated containing eight genes, including a gene, muscarinic acetylcholine receptor M5 (Chrm5), that has been associated with burrowing, likely acting in the reward system in the brain through dopamine release. Thus, increased digging could be caused by increasing the reward for digging. This study has three aims: 1. To characterize expression levels of 7 additional genes in the QTL using quantitative RT-PCR; 2. To chararacterize the tissue-specific distribution of Chrm5 in brains of both species and hybrids using staining techniques; and 3. To introduce oldfield mouse Chrm5 into deer mouse brain using viral-vector-mediated gene transfer and to assay behaviors in the resulting mice. It is hypothesized that increasing Chrm5 expression level in the deer mouse should increase burrowing behavior. By studying the precise mechanisms that produce behavioral changes between species, it should be possible to learn how behavior evolves as well as gain a better understanding of how the brain works. The outcomes of this research will improve our overall understanding of behavioral diversity in animals, and will be used to create educational materials for the Harvard Museum of Natural History. Finally, since Chrm5 is also implicated in nicotine use, studies of this receptor could potentially be applied to the general study of addiction.

该项目的主要目标是了解导致行为自然变异的遗传和神经生物学机制。 该研究将集中在两种密切相关的北美小鼠（Peromyscus属）之间的穴居行为差异：oldfield小鼠一贯挖掘长的多隧道洞穴，而姐妹物种鹿鼠则用一个隧道建造短洞穴。这种洞穴结构的物种特异性差异是可遗传的，并且已经确定了可能参与调节洞穴结构的基因。 这项研究提出操纵每个物种的基因表达，以确定基因如何在大脑中发挥作用，从而产生导致不同洞穴结构的行为差异。 已经分离出含有8个基因的QTL，其中包括一个基因，毒蕈碱乙酰胆碱受体M5（Chrm 5），该基因与穴居有关，可能通过多巴胺释放在大脑的奖励系统中起作用。因此，挖掘的增加可能是通过增加挖掘的奖励引起的。 本研究有三个目的：1.利用定量RT-PCR技术对QTL中另外7个基因的表达水平进行了表征; 2.利用染色技术研究Chrm 5在两个物种及其杂种脑中的组织特异性分布。利用病毒载体介导的基因转移技术将老年小鼠Chrm 5基因导入鹿鼠脑内，并观察其行为学变化。据推测，增加鹿鼠中的Chrm 5表达水平应增加穴居行为。通过研究物种之间产生行为变化的精确机制，应该可以了解行为如何进化，并更好地了解大脑如何工作。这项研究的结果将提高我们对动物行为多样性的整体理解，并将用于为哈佛自然历史博物馆制作教育材料。最后，由于Chrm 5也与尼古丁的使用有关，因此对这种受体的研究可能适用于成瘾的一般研究。