Dorsal Raphe Astrocytes Orchestrate Social Bonding via Serotonergic Modulation of Prefrontal Circuits

Social behaviors such as bonding, preference, and social memory are essential for life in groups and are tightly regulated by complex neural circuits. While neurons have traditionally been the focus, emerging evidence highlights astrocytes as active regulators of complex behaviors. Here, we identify astrocytes in the dorsal raphe (DR) nucleus as critical modulators of social bonding in mice. Selective activation of DR astrocytes was sufficient to drive a shift in social preference toward an unfamiliar conspecific, which was not initially preferred, promoting prosocial attachment (bonding). Activation of DR astrocytes increases the motivational drive for social interaction by promoting memory recall of bonded individuals and outweighing social novelty preference. These effects were not replicated by direct activation of DR serotonergic neurons, underscoring the unique role of astrocytes. At network level, DR astrocyte activation leads to local modulation of serotonin (5-HT) neurons, promoting 5-HT release in the medial prefrontal cortex (mPFC) and long-range control of cortical activity. Thus, DR astrocytes enhanced mPFC neuronal firing during interactions with bonded individuals. This targeted modulation refines social identity encoding without affecting baseline excitability or general sociability. These findings reveal a novel astrocyte-driven mechanism underlying bond formation, positioning DR astrocytes as crucial components in the regulation of social behaviors.