Role of Mesolimbic dopaminergic Circuit in Social Decision-Making

초록

Motivation is crucial for animals' goal-directed behavior, aiding them in persevering though challenges. In social animals, social interaction serve as a potent motivator to surmount obstacle. Nevertheless, the precise mechanism underpinning social motivation remains unclear. We designed an effort-based social decision-making (ESDM) task focusing on 'Effort' choices. Male mice consistently chose to approach females, even when it required necessitated a barrier (EFBO), especially on the last day of the task. We delved into dopamine receptor gene expression in the nucleus accumbens (NAc), a pivotal region for dopamine reception. Interestingly, Drd1a gene expression was notably elevated in the EFBO group. Furthermore, direct infusion of a D1R antagonist into the NAc, resulted in reduced 'Effort' choice levels. We also monitored real-time in vivo dopamine signals in the NAc during the task, noting that dopamine signals associated with 'Effort' choices were strengthened on the last day. Given the central role of the ventral tegmental area (VTA) in dopamine release, we conducted optogenetic manipulations of the VTA→NAc circuit. We found that it caused significant changes in 'Effort' choice levels. Finally, we discovered that heightened dopamine levels induce histone H3 dopaminylation at the Drd1a gene promoter region, thereby reinforcing ESDM behavior. These findings suggest that D1-cells within the mesolimbic dopaminergic system may play a crucial role in effort-based decision-making for social reward.