Elucidating the role of VTA D2 autoreceptors in FXS-related abnormal sociability*
Bojana Zupan (Psychological Science)
The mouse model of Fragile X Syndrome (FXS), the largest single-gene cause of autism, recapitulates many autism-related behaviors including abnormal sociability and behavioral inflexibility. Our lab has shown, however, that hyperactivity and abnormal sociability occur in genetically unaffected mice derived from heterozygous females, suggesting that reduction in parental FMR1 expression has an intergenerational programming effect on offspring neurodevelopment. One putative target of such programming is the dopamine autoreceptor 2 (D2aR), whose reduced expression in the ventral tegmental area (VTA) is associated with behavioral dysfunction. To assess whether this reduced expression is sufficient to induce the previously observed behavioral phenotype, we will eliminate or reduce D2aR in VTA dopaminergic neurons both during development and adulthood using a cre/lox breeding design as well as a viral vector approach. This project will involve extensive animal handling, behavioral testing, and immunohistochemical analysis. Opportunity to perform surgical manipulation and tissue harvest will depend on candidate’s degree of experience/comfort with invasive procedures. The animal breeding phase of this project has already begun and data acquisition and analysis are expected to continue into the 2018/2019 academic year. Students interested in contributing to this project across multiple semesters are encouraged to apply.
Prerequisites: Previous rodent handling and research experience as well as successful completion of Research Methods in Physiological Psychology preferred.
How should students express their interest in this project? Students are requested to submit a brief statement of interest (200 word limit, by email). Top candidates will be contacted by Prof. Zupan to set up an in-person interview.