The goal of this project is to develop approaches to manipulate gene function in non-traditional animal models to understand the role of the vasopressin receptor gene in regulating social behavior. Silencing or disrupting genes in mice has also helped to understand how certain genes influence behaviors. However, mice are not ideal for studying many aspects of behaviors, including social behaviors. Comparative biology uses a wide variety of species with particular characteristics that make them ideal for studying the particular questions. For example, prairie voles are a monogamous rodent species that have been used to understand how molecules act within certain brain circuits to promote social bonding. Hamsters are more solitary and display robust territorial behavior, and have been used to investigate the roles of brain molecules in social communication. However, the utility of these non-traditional species for understanding the roles of specific genes in controlling behavior has been limited because of the inability to manipulate genes. The goal of this project is to use parallel approaches in hamsters and prairie voles to silence the vasopressin receptor gene using two different approaches. One approach will effectively silence vasopressin receptor gene expression, while the other will introduce a mutation in the gene, making it ineffective. By manipulating the expression of this gene, more insights into its role in regulating social behaviors, including social bonding and territorial behaviors will be achieved. Furthermore, the development of these approaches should be applicable to a wide range of mammalian species that are useful for studying different questions. The development of these approaches in hamsters and prairie voles will be transformative for comparative behavioral neuroscience. This project will engage students, ranging from high school to graduate school, in comparative studies addressing the underlying neurogenetics of social behavior. Also, partnerships with Zoo Atlanta will be instrumental in developing new research and educational exhibits that will serve to educate the public on the neurogenetics of social behavior.
This Project was a collaboration between Dr. Elliott Albers at Georgia State University, and Larry Young at Emory University in Attanta. The goal of this project was to create transgenic prairie voles and hamsters using two separate approaches: i) viral vector mediated gene transfer into embryos to express shRNA that would suppress vasopressin receptor expression and ii) by using zinc finger nucleases injected into the embryos to selectively mutate the vasopressin receptor. Both prairie voles and hamsters have become important model organisms to study the brain mechanisms regulating social behavior. In particular, vasopressin receptor has been shown to modulate social communication, territorial behavior and aggression in hamsters and pair bonding in monogamous prairie voles. The ability to genetically alter the genome, specifically genes involved in regulating behavior, in non-traditional animal models such as prairie voles and hamsters would be a significant advancement for the field of behavioral neuroendocrinology. Efforts to generate transgenic animals were run in parallel at Emory (for prairie voles) and at Georgia State (for hamsters). Despite our early success creating a transgenic prairie vole expressing GFP in 2009, unfortunately we were not able to create transgenic or mutated prairie voles or hamsters during the funding period. Our success was hampered by different aspects of embryo culture techniques and reproductive physiology in hamsters and voles compared to mice. Although we were not successful at our initial goal, throughout the process we have learned a great deal and we remain committed to genetically engineering both of these non-traditional rodents which are invaluable model organisms for behavioral neuroscience. The insights gained during the funding period will be invaluable as we move forward to achieve our goal. For example, techniques for increasing the yield of embryos in prairie voles were published and the optimum conditions for culturing and transferring hamster embryos were established. Two graduate students and one postdoctoral fellow have been trained during the funding period. A transgenic core facility, run by Chengliu Jin (whose position was made possible by this grant) has been established at Georgia State University. Both Drs. Albers and Young remain committed to the original goals of this proposal and are continuing our pursuit. The achievements made possible by the support of the NSF grant have laid the foundation for future exciting studies using transgenic hamsters and voles.
