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

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.