Measuring social withdrawal: Using semi-natural social environments to identify translational measures in mice

Excessive social withdrawal is a symptom of multiple neuropsychiatric disorders, greatly impacting the quality of life. The heritability of neuropsychiatric disorders suggests that we can search for their cause in the genetics. Since humans and other animals show overlapping genes and social behavior, we can utilize model organisms to study the genetics behind social withdrawal. Conventional tests for social behavior, in which two interacting animals are observed in an artificial environment, have proven to be difficult to replicate and insufficient to develop a treatment for the patients. There is a need for a reliable and validated test for complex social behaviors. Thus, in this thesis we aim to develop a generalizable and ethologically valid method to reliably quantify social withdrawal in mice, laying a foundation for future translational research. Our methods focus on measuring social group-behavior in a semi-natural environment, in which the mice could interact freely, over a period of multiple days. We have shown that we can replicate findings from earlier research, which used conventional tests, in our semi-natural environments. Further, we were able to replicate the results from our own experiments in another laboratory, showing the robustness of our methods. We have demonstrated that our methods can be used to study human risk genes for excessive social withdrawal in genetic and pharmacological mouse models. This showed that a specific dopamine receptor impacts social behavior in different species. With this we provide a foundation for future translational research.