Hypothalamic plasticity for alloparenting in male mice

O'Neill, P. T.; Yan, R.; Wang, Y.; Wang, Q.; Yin, L.; Lhamo, G.; Rhodes, D. J.; Little, J.; Cheng, H.; Chen, L.; Shoham, S.; Chen, X.; Froemke, R. C.; Lin, D.

doi:10.64898/2026.10.21.760822

bioRxiv · 10.64898/2026.10.21.760822

Hypothalamic plasticity for alloparenting in male mice

O'Neill, P. T.·Yan, R.·Wang, Y.·Wang, Q.·Yin, L.·Lhamo, G.·Rhodes, D. J.·Little, J.·Cheng, H.·Chen, L.·Shoham, S.·Chen, X.·Froemke, R. C.·Lin, D.

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Abstract

Repeated exposure to young can induce caregiving in virgin female mice, a phenomenon known as pup sensitization, but whether virgin males can similarly acquire parental behavior and the neural mechanisms underlying this transition remain unclear. We show that 7 days of continuous pup exposure reliably converts virgin adult male mice to a parental state. This transition requires calcitonin receptor (CalcR)-expressing neurons in the medial preoptic area (MPOA): silencing MPOACalcR neurons disrupts both the acquisition and expression of paternal behavior, whereas optogenetic activation of GABAergic MPOACalcR neurons promotes caregiving in virgin males. Longitudinal two-photon calcium imaging reveals that MPOACalcR neurons develop enhanced pup-selective responses as males transition to a parental state. Moreover, CalcR signaling in the MPOA promotes synaptic potentiation and facilitates the emergence of parental behavior. These results identify an experience-dependent hypothalamic plasticity mechanism that enables parental behavior in non-father males.

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O'Neill, P. T., Yan, R., Wang, Y., Wang, Q., Yin, L., Lhamo, G., Rhodes, D. J., Little, J., Cheng, H., Chen, L., Shoham, S., Chen, X., Froemke, R. C., Lin, D.. 2026-10-22. Hypothalamic plasticity for alloparenting in male mice. https://doi.org/10.64898/2026.10.21.760822

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