BEYOND REWARD: A11 DOPAMINERGIC NEURONS DRIVE SOCIAL MOTIVATION IN MICE

Social interaction among conspecifics is the key player of a wide range of activities, including behavior, and survival. It is regulated by diverse neuronal subpopulations and complex neural circuits that relay motivational and emotional information, which mostly orchestrate the dopaminergic systems. Recent findings demonstrate that dopaminergic A11 neurons might integrate motivational and behavioral states, however their involvement in mammalian social interaction regulation remained elusive. Here, we aimed to identify the role of tyrosine hydroxylase (Th)-expressing dopaminergic A11 neuron activity in modulating social interaction and motivation in mice. To investigate the central regulation of social interaction via A11 neurons, we optogenetically activated A11 neurons of male Th-cre mice via intracranially delivering rAAV2/1-EF1a-DIO-hChR2(H134R)-EYFP-WPRE-HGHpA and used rAAV2/1-CAG-DIO-GFP (n=6/group). Th-cre male mice performed female and intruder interaction tests. Our results indicate that optogenetic activation of A11 neurons significantly enhanced interaction with female mice, which suggests increased social motivation. Similarly, increased intruder interaction upon A11 neuron activation is the key evidence of improved investigation and decreased avoidance (p<0.05). We further investigated whether A11 neuron activation is essential to drive motivation alone. To do this, Th-cre male mice performed conditioned place preference test where mice were monitored for their time in the chamber with optogenetic A11 neuron stimulation. The findings suggest that mice significantly preferred the chamber where optogenetic A11 neuron stimulation was applied (p<0.05). Taken together, our findings indicate that dopaminergic A11 neurons are key players of social interaction, and these neurons are sufficient to drive motivation even in the absence of a rewarding cue.