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

该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。这项研究将集中在两种密切相关的北美小鼠（Peromyscus属）之间挖洞行为的差异：老田鼠一贯挖掘长而多隧道的洞穴，而其姊妹物种鹿鼠则建造只有一条隧道的短洞穴。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。本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，从而产生导致不同穴居结构的行为差异。一个含有8个基因的QTL已经被分离出来，其中包括一个基因，毒蕈碱乙酰胆碱受体M5 (Chrm5)，该基因与挖洞有关，可能通过释放多巴胺在大脑的奖励系统中起作用。因此，增加挖掘可以通过增加挖掘的奖励来引起。本研究有三个目的：1。利用定量RT-PCR技术表征QTL中另外7个基因的表达水平；2. 利用染色技术表征两种和杂交种大脑中Chrm5的组织特异性分布；和3。利用病毒载体介导的基因转移方法将老田小鼠Chrm5导入鹿小鼠脑内，并测定其行为。据推测，增加鹿鼠的Chrm5表达水平应该会增加挖洞行为。通过研究物种之间产生行为变化的精确机制，应该有可能了解行为是如何进化的，并更好地了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，并将用于为哈佛自然历史博物馆制作教育材料。最后，由于Chrm5也与尼古丁使用有关，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.