Role of Mesocorticolimbic Circuitry in Social Decision Making

초록

Motivation is essential for goal-directed behavior, enabling animals to persist in the face of challenges. In social animals, social interaction serves as a potent motivator. However, how social rewards shape motivational choices to invest effort remains poorly understood. To address this, we developed an effort-based social decision-making (ESDM) task in which mice chose between a neutral and an effortful option. Male mice consistently chose to overcome a barrier to access a female, despite equivalent reward availability. We observed significant upregulation of Drd1a, which encodes the D1 dopamine receptor, in the nucleus accumbens (NAc), a key region for dopamine signaling. Consistently, pharmacological blockade of D1 receptors in the NAc reduced effort choice levels. In vivo fiber photometry analysis revealed that NAc dopamine signals during the decision-making period of effortful choice trials from the first to the final day. Notably, effort choice level was further enhanced by optogenetic activation of VTA–NAc projections and abolished by D1 receptor blockade. Finally, we found that increased dopamine activity induced H3Q5dopaminylation at the Drd1a promoter in the NAc, reinforcing effortful social choice. These findings suggest that effort-based social decision-making is regulated by dopamine-dependent epigenetic mechanisms within D1R-expressing neurons of the mesolimbic pathway.