Subthalamic nucleus optogenetic inhibition reduces motivation for social interactions

Dysregulation of social motivation can lead to social maladjustment, relationship degradation, and is common in many neuropsychiatric disorders such as autism or depression. It is thus very important to better understand the neurobiological substrate underlying this dysregulation of motivation. The Subthalamic Nucleus (STN) has been shown to be a crucial brain region to regulate motivation and emotions. STN lesions induce impairments in various aspects of social behavior in rats, including reduced motivation for rewarding positive ultrasonic vocalizations (USV), non-recognition of emotional vocalizations, and impairment in social recognition memory. Thus, alterations in STN function could lead to deficits in social motivation. Here, we directly assessed STN involvement STN in social motivation by employing an operant protocol using social interaction as a reward via an automatic door and a grid. Non-isolated rats were trained to self-administer social interactions with familiar or unfamiliar peers (i.e., cagemates or stranger rats) in a standard fixed ratio 1 schedule of reinforcement, and then in a progressive ratio task. The involvement of STN in these processes has been assessed by optogenetic STN neuronal inhibition. The results show that rats are working for both types of peers (i.e., cagemates or stranger rats) and that STN optogenetic inhibition decreased the motivation to work for a social interaction with a peer. These results confirm that non-isolated rats can work in an operant protocol for social interactions with different types of peers and further position the STN as a critical actor in the regulation of social motivation.