Serotonin modulates nucleus accumbens circuits to suppress aggression

Zhang, Z.; Touponse, G. C.; Alderman, P. J.; Yassine, T.; Pomrenze, M. B.; Harris, T. W.; Shank, A. N.; Malenka, R. C.; Eshel, N.

doi:10.1101/2025.11.26.690732

bioRxiv · 10.1101/2025.11.26.690732

Serotonin modulates nucleus accumbens circuits to suppress aggression

Zhang, Z.·Touponse, G. C.·Alderman, P. J.·Yassine, T.·Pomrenze, M. B.·Harris, T. W.·Shank, A. N.·Malenka, R. C.·Eshel, N.

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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 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.

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Zhang, Z., Touponse, G. C., Alderman, P. J., Yassine, T., Pomrenze, M. B., Harris, T. W., Shank, A. N., Malenka, R. C., Eshel, N.. 2025-11-27. Serotonin modulates nucleus accumbens circuits to suppress aggression. https://doi.org/10.1101/2025.11.26.690732

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