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

这个项目的主要目标是了解导致行为自然变化的遗传和神经生物学机制。这项研究将重点放在两种关系密切的北美老鼠(Permyscus属)之间的洞穴行为上的差异：奥德菲尔德老鼠一直在挖掘长的、多隧道的洞穴，而姊妹物种鹿鼠则用单隧道建造短洞穴。洞穴结构的这种物种特异性差异是可遗传的，并且已经确定了可能参与调控洞穴结构的基因。这项研究建议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。已经分离出一个包含八个基因的QTL，其中包括一个与穴居有关的基因，即M胆碱乙酰胆碱受体M5(Chrm5)，可能通过释放多巴胺作用于大脑的奖赏系统。因此，增加挖掘可能是因为增加了对挖掘的奖励。本研究有三个目的：1.用定量RT-PCR方法研究另外7个基因在QTL中的表达水平；2.用染色技术研究chrm5基因在不同物种和杂交种中的组织特异性分布；3.通过病毒载体介导的基因转移将Oldfield小鼠chrm5基因导入鹿小鼠脑内，并对其行为进行检测。据推测，在鹿小鼠中增加chrm5的表达水平应该会增加洞穴行为。通过研究在物种之间产生行为变化的精确机制，应该可以了解行为是如何进化的，以及更好地理解大脑是如何工作的。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，并将被用于为哈佛自然历史博物馆创建教育材料。最后，由于chrm5也与尼古丁的使用有关，对这种受体的研究可能会应用于成瘾的一般研究。

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.