SCHOOLING AS A NOVEL BEHAVIORAL ASSAY TO PROBE NEURODEVELOPMENTAL CHANGES FROM FMRP KNOCKDOWN AND VPA EXPOSURE IN THE XENOPUS LAEVIS MODEL FOR AUTISM
Mashfiq Hasan1, Tyler Wishard2, Eric James1, Arseny Khakhalin1, Carlos Aizenman1.
1Brown University, Providence, RI, 2University of California, San Diego, La Jolla, CA.
The development of novel animal models to study neurodevelopmental disorders such as autism is critical for understanding the basic biology underlying these disorders. The growing nervous system of Xenopus laevis tadpoles is an established animal model for neurodevelopment. Recent work in our laboratory, and in that of our collaborators, has explored two novel neurodevelopmental interventions resulting in abnormal formation of neural circuits in Xenopus tadpoles. Both exposure to valproate (VPA), a known teratogen associated with elevated incidence of autism following prenatal exposure, and knockdown of FMRP, a key protein in Fragile X Syndrome, a leading monogenetic cause of autism in humans, result in abnormally formed neural circuits in Xenopus tadpoles. One common feature of autism is the presence of sensory integration problems as well as deficits in social interaction. Here we show a novel test for assaying sensory integration and social interaction in Xenopus tadpoles, by analyzing a multisensory aggregation behavior known as schooling, partially mediated by the optic tectum. We will assess the effects of VPA exposure and FMRP misexpression on this behavior. We hypothesize that VPA and FMRP misexpression will lead to abnormal schooling behavior in tadpoles. Our behavioral protocol analyzes inter-tadpole distances and co-orientation of nearby tadpoles to assess schooling. By studying an analogue of human social behavior in the Xenopus laevis model, we hope to provide a novel means of comparing human neuronal changes to an animal model and support further experiments using Xenopus laevis tadpoles.