Astrocytes amplify cortical dopamine to encode winning memory in male mice

초록

Memories of winning experiences reinforce dominance hierarchies, yet mechanisms encoding these long-lasting "winning memories" remain unclear. Here, we introduce a combined Tube & Conditioned Place Preference (CPP) paradigm and applied fiber photometry, genetic manipulations, and optogenetics to characterize social competition between adult male mice. We found that initial victories trigger dopamine D2 receptor-mediated calcium activities of astrocytes in the medial prefrontal cortex (mPFC) and subsequent glutamate release. This mechanism enhances dopaminergic responses in mPFC neurons projecting to the nucleus accumbens (NAc), thereby consolidating winning memories. Upon ablation of D2 receptors in mPFC astrocytes, this effect is abolished, hindering generation of new dominance memories and a stable social hierarchy. Our findings reveal an astrocyte-driven mechanism by which mesocortical dopamine signaling reinforces victory-related neural plasticity, and provide broad insights into the cellular basis of social dominance and its underpinnings in motivational and affective disorders.

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