VALIDATION OF A NEW MOUSE MODEL FOR AUTISM SPECTRUM DISORDER RESEARCH: Suelen Baggio

Autism spectrum disorder (ASD) embraces several behavioral and sensorimotor alterations. ASD is associated with neurodevelopmental impairments. Considering the important role of thalamocortical connections in processing sensory information and producing behavioral responses, impaired thalamic development can contribute to ASD symptoms. However, this assumption is poorly supported experimentally. Therefore, this study aims to understand the role of the thalamus in the pathogenesis of ASD using a new mouse model, a strain developed in our laboratory in which the regulator of thalamic maturation TCF7L2 is knocked out postnatally. To validate ASD-associated phenotypes, we analyzed the mice's behavioral profile through the following behavioral tests: Open field, marble-burying test, buried food test, and Eco-HAB. TCF7L2 KO mice present a decrease in social performance, not interacting with other mice during the exploration of a cage and spending less time in the compartment containing social scent. They show a decrease in grooming behavior and no difference in repetitive behavior. In addition, they do not show impairments in locomotor activity or olfactory function, according to the Open field and Buried Food tests. These results corroborate a hypothesis that thalamic dysfunctions originating from perinatal development can be a primary cause of social deficits and behavioral inflexibility in ASD.