Altered neural activity in the mesoaccumbens pathway underlies impaired social reward processing inShank3-deficient rats

Abstract

AbstractSocial behaviors are crucial for human connection and belonging, often impacted in conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (VTA and NAc) plays a pivotal role in social behavior and is implicated in ASD. However, the impact of ASD-related mutations on social reward processing remains insufficiently explored. This study focuses on theShank3mutation, associated with a rare genetic condition and linked to ASD, examining its influence on the mesoaccumbens pathway during behavior, using theShank3-deficient rat model. Our findings indicate thatShank3-deficient rats exhibit atypical social interactions and have difficulty adjusting behavior based on reward values, associated with modified neuronal activity of VTA dopaminergic and GABAergic neurons and reduced dopamine release in the NAc. Moreover, we demonstrate that manipulating VTA neuronal activity can normalize this behavior, providing insights into the effects ofShank3mutations on social reward and behavior, and identify a potential neural pathway for intervention.