Multi-integrative role of oxytocin receptor signaling: effect on social behavior and social interaction disorders – MIRORS

Disorders affecting social behaviors, such as autism spectrum disorders (ASD), are complex neurodevelopmental disorders involving deficits in social interaction and communication. To date, no pharmacological treatment that improve social symptoms exists for ASD, and the only therapeutic options rely on costly behavioral intervention programs with limited beneficial effects. Oxytocin and its receptor are key determinant players of social behaviors with therapeutic potential for social interaction deficits. Oxytocin receptor is expressed in specific brain structures and cell types in the central nervous system. Here, we propose i) to dissect the role of oxytocin receptor in these structures, spanning from olfactory neurons to glial cells and neurons in interconnected central brain areas, and ii) establish a therapeutic framework of exogenous intranasal oxytocin administration in a mouse model of autism. We will identify how oxytocin receptor in the mouse olfactory system modulates social interactions, determine the modulatory role of oxytocin receptor centrally, in both neurons and astrocytes and use administration of exogenous oxytocin in a well-established and mouse model of ASD and Fragile X syndrome. Overall, our project will provide essential novel information on how oxytocin modulate social signals and brain activity to enable social interactions, providing therapeutic levers in the context of sociability disorders.