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Altered Neural Activity in the Mesoaccumbens Pathway Underlies Impaired Social Reward Processing in Shank3‐Deficient Rats
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Altered Neural Activity in the Mesoaccumbens Pathway Underlies Impaired Social Reward Processing in Shank3‐Deficient Rats
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Journal Article
Altered Neural Activity in the Mesoaccumbens Pathway Underlies Impaired Social Reward Processing in Shank3‐Deficient Rats
2025
Overview
Social behaviors are crucial for human connection and belonging, often impacted by conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (ventral tegmental area (VTA) to the nucleus accumbense (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 the Shank3 mutation, associated with a rare genetic condition and linked to ASD, examining its influence on the mesoaccumbens pathway during behavior, using the Shank3‐deficient rat model. Our findings indicate that Shank3‐deficient rats exhibit atypical social interactions, associated with altered neuronal activity of VTA dopaminergic and GABAergic neurons and reduced dopamine release in the NAc. Moreover, they demonstrate that manipulating VTA neuronal activity can normalize this behavior, providing insights into the effects of Shank3 mutations on social reward processing and identifying a potential neural pathway for intervention. This study examines the effects of Shank3 mutation on the mesoaccumbens pathway using a Shank3‐deficient rat model. The findings reveal altered social reward processing in these rats, accompanied by changes in dopaminergic and GABAergic neural activity within the ventral tegmental area (VTA) and dopamine release in the nucleus accumbense (NAc). Modulating VTA activity restores typical social behavior, pionting to a potential neural pathway for intervention.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Autism
/ Autism Spectrum Disorder - genetics
/ Autism Spectrum Disorder - pathology
/ Autism Spectrum Disorder - physiopathology
/ Autism Spectrum Disorder - psychology
/ Brain
/ dopamine
/ Dopaminergic Neurons - metabolism
/ GABAergic Neurons - metabolism
/ Male
/ Mutation
/ Nerve Tissue Proteins - deficiency
/ Nerve Tissue Proteins - genetics
/ Neural Pathways - physiopathology
/ Nucleus Accumbens - cytology
/ Nucleus Accumbens - pathology
/ Nucleus Accumbens - physiopathology
/ Rats
/ Reward
/ Shank3
/ Ventral Tegmental Area - cytology
