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

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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.