Increased c-Fos expression in lateral habenula during social transmission of negative valence in prairie voles

草原田鼠在社会性传播负面情绪的过程中,侧缰核中 c-Fos 表达增加

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Abstract

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 show deficits in social salience and reciprocal affective responses. Social learning implicates the basolateral amygdala (BLA), anterior cingulate cortex (ACC), and anterior insula (AI). The lateral habenula (LHb), a brain area renowned for its role in negative reinforcement learning, has not been yet extensively studied in the domain of social learning. METHODS: We developed a fear conditioning by proxy paradigm called ‘social transmission of negative valence’ (STNV) and tested 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 h after observation. We measured observers’ freezing time, self-grooming, rearing, and ultrasonic vocalizations emitted as signs 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 ultrasonic vocalization frequency compared to controls. Socially-conditioned observers showed increased c-Fos expression in the LHb, BLA, ACC and AI compared to controls. LIMITATIONS: The c-Fos findings are correlational and additional experiments involving chemo- or optogenetic inhibition or excitation of LHb neurons in observers are necessary for causality confirmation. CONCLUSIONS: We found that the LHb is co-activated with other key areas during social learning in prairie voles. These findings extend the traditional view of the LHb as an area involved in negative reinforcement learning and position it as a critical area for social affect. This offers a fresh perspective on the neural mechanisms of social affect and opens a new line of inquiry into brain dysfunction of social salience in neurodevelopmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13229-026-00712-5.

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