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.
Data availability
Data generated in this study are provided in a Source Data file and on Zenodo (https://doi.org/10.5281/zenodo.18236031). Source data are provided with this paper.
Code availability
Custom codes are deposited on Zenodo (https://doi.org/10.5281/zenodo.18235848).
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Acknowledgements
We thank Daniel F. Cardozo Pinto for useful discussions; Amber Osterman and May Wang for technical support; and Zane C. Norville for advice on the SIMBA software. This work was supported by philanthropic funds donated to the Nancy Pritzker Laboratory at Stanford University and to R.C.M. from the Gatsby Initiative for Brain Development and Psychiatry and the NeuroChoice Initiative of the Wu Tsai Neurosciences Institute. N.E. was supported by NIH grants K08MH123791 and R01MH138645, a Brain & Behavior Research Foundation Young Investigator Grant, a Burroughs Wellcome Fund Career Award for Medical Scientists, a Stanford NeuroChoice Initiative Pilot Award, and a Simons Foundation Bridge to Independence Award. N.E. and R.C.M. are also both supported by ARIA (Aligning Research to Impact Autism). G.C.T. was supported by the Berg Scholars program at Stanford School of Medicine. M.B.P. was supported by NIH grant K99 DA056573. Z.Z. was supported by the Wu Tsai Neurosciences Institute.
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Z.Z., R.C.M., and N.E. conceived the study and designed the experiments. Z.Z. performed the neural recording and optogenetic experiments and analyzed data. Z.Z., G.C.T., P.J.A. and A.N.S. performed the surgeries. T.Y., T.W.H., Z.Z. and P.J.A. performed histology. M.B.P., G.T., and Z.Z. performed the pharmacological experiments. The manuscript was written by Z.Z, R.C.M., and N.E and edited by all authors.
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R.C.M. is on the scientific advisory boards of MapLight Therapeutics, Definium Therapeutics, and Aelis Farma. N.E. is a consultant for Boehringer Ingelheim. Z.Z., G.C.T., P.J.A., T.Y., T.W.H. M.B.P. and A.N.S. declare no competing interests.
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Zhang, Z., Touponse, G.C., Alderman, P.J. et al. Serotonin modulates nucleus accumbens circuits to suppress aggression in mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69254-x
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DOI: https://doi.org/10.1038/s41467-026-69254-x
