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bioRxiv · 10.64898/2026.04.03.716295

Sustained effect of MPOA Penk neurons underlies progression through consummatory mating behavior in male mice

Tsuneoka, Y.·Kanno, K.·Narikiyo, K.·Funato, H.
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Abstract

Male rodent sexual behavior progresses from appetitive to consummatory mating, implying a sustained internal motivational state. Estrogen receptor 1 (Esr1)-expressing neurons in the medial preoptic area (MPOA) regulate discrete mating actions, but how motivational drive is sustained across mating remains unknown. Here, we identify an MPOA Esr1+ neuronal subtype marked by proenkephalin (Penk) that promotes the transition from mount to intromission. Male mice exhibited a bimodal progression to consummatory mating, and Penk-expressing neurons represented the predominant population recruited for consummatory behaviors. In sexually active males, Penk+ neurons exhibited sustained Ca{superscript 2} dynamics. Chemogenetic manipulation selectively enhanced female-directed consummatory behaviors without affecting intermale interactions. Optogenetic activation of Penk+ neurons or their terminals promoted consummatory behavior over a behaviorally relevant timescale. Thus, MPOA Penk+ neurons provide a circuit substrate for a sustained internal state that ensures successful mating progression.

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Tsuneoka, Y., Kanno, K., Narikiyo, K., Funato, H.. 2026-04-06. Sustained effect of MPOA Penk neurons underlies progression through consummatory mating behavior in male mice. https://doi.org/10.64898/2026.04.03.716295

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