Concerted actions of distinct serotonin neurons orchestrate female pup care behavior

Xiao, S. A.; Chen, C. C.; Horvath, P.; Tsai, V.; Cardenas, V. M.; Biderman, D.; Deng, F.; Li, Y.; Linderman, S.; Dulac, C.; Luo, L.

doi:10.1101/2025.07.31.667987

bioRxiv · 10.1101/2025.07.31.667987

Concerted actions of distinct serotonin neurons orchestrate female pup care behavior

Xiao, S. A.·Chen, C. C.·Horvath, P.·Tsai, V.·Cardenas, V. M.·Biderman, D.·Deng, F.·Li, Y.·Linderman, S.·Dulac, C.·Luo, L.

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Abstract

In many mammalian species, female behavior towards infant conspecifics changes across reproductive stages. Sexually naive females interact minimally or aggressively with infants, whereas the same animals exhibit extensive care behavior, even towards unrelated infants, after parturition1-6. Here, we discovered that two distinct sets of serotonin neurons collectively mediate this dramatic transition in maternal behavior--serotonin neurons projecting to the medial preoptic area (mPOA) promote pup care in mothers, whereas those projecting to the bed nucleus of the stria terminalis (BNST) suppress pup interaction in virgin female mice. Disrupting serotonin synthesis in either of these subpopulations or stimulating either subpopulation is sufficient to toggle pup-directed behavior between that displayed by virgin females and that of lactating mothers. In virgin female mice, the first pup interaction triggers an increase in serotonin release in BNST but a decrease in mPOA. In mothers, serotonin activity becomes greatly elevated in mPOA during pup interactions. Acute interruption of serotonin signaling locally in either mPOA or BNST disrupts the stage-dependent switch in pup care. Together, these results highlight how functionally distinct serotonin subpopulations orchestrate social behaviors appropriate for a given reproductive state, and suggest a circuit logic for how a neuromodulator coordinates adaptive behavioral changes across life stages.

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Xiao, S. A., Chen, C. C., Horvath, P., Tsai, V., Cardenas, V. M., Biderman, D., Deng, F., Li, Y., Linderman, S., Dulac, C., Luo, L.. 2025-08-01. Concerted actions of distinct serotonin neurons orchestrate female pup care behavior. https://doi.org/10.1101/2025.07.31.667987

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