Serotonin modulates nucleus accumbens circuits to suppress aggression in mice.

Zhang, Zihui; Touponse, Gavin C; Alderman, Pia J; Yassine, Teema; Pomrenze, Matthew B; Harris, Troy W; Shank, Amei N; Malenka, Robert C et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

Serotonin (5-hydroxytryptamine; 5HT) has long been considered anti-aggressive, but the mechanisms by which 5HT regulates downstream circuits to control aggression remain unclear. Combining fiber photometry, optogenetics, and miniaturized microscope recordings in double-transgenic male mice, we find that 5HT levels ramp up in the nucleus accumbens during aggression, inhibiting a subset of D1 medium spiny neurons to suppress attacks. Our results reveal a novel 5HT-mediated neuromodulatory mechanism for limiting aggressive behavior.

Medical subject headings