Increased c-Fos Expression of Lateral Habenula during Social Transmission of Negative Valence in Prairie Voles

Background Social learning is the process of acquiring social skills, new information, or associating negative or positive valence to a context through the observation of others and through direct social interaction with others. Neurodevelopmental disorders such as autism spectrum disorder or ASD show deficits in social salience and reciprocal affective responses. Social learning is known to implicate brain areas that relate to both aspects of social salience and affective empathy such as basolateral amygdala (BLA), anterior cingulate cortex (ACC), and anterior insula (AI). Lateral Habenula (LHb), a brain area renowned for its role in negative reinforcement learning and reward prediction error has not been yet extensively studied in the domain of social learning. Methods We developed an adapted version of fear conditioning by proxy paradigm called “Social Transmission of Negative Valence” or STNV and tested social rodent species prairie voles on the task. Observers experienced negative social conditioning through a proxy cage mate that served as the demonstrator during retrieval of a cued fear memory. Observers went through a social memory recall session 24 hours after observation. We measured observers’ freezing time, self-grooming, rearing, and the range of frequency of ultrasonic vocalizations emitted as sign of distress. We also quantified immediate early gene translation as a proxy for neural activity using c-Fos immunochemistry 80 min after observing demonstrators going through memory recall. Results Socially conditioned observers that were exposed to the fear-conditioned demonstrators displayed increased freezing time, self-grooming, and rearing during social recall sessions compared to control observers. They also displayed higher USVs frequency on average compared to controls. Socially conditioned observers showed increased c-Fos expression in the LHb and BLA, ACC and AI, in comparison to controls. Conclusions Prairie voles can be conditioned to threat through social transmission of negative valence. They activate brain areas known to be involved in affective processes and social salience. LHb can be another area of interest for neural correlates of social learning and may further be investigated as a part of a Social Affect Salience Network.