A male-biased hypothalamic circuit modulates postmating sleep suppression in mice.

Many species display mating-related sleep suppression to maximize reproductive success, yet the underlying neural mechanisms in mammals remain unclear. Here, we report that male mice exhibit delayed sleep onset and reduced sleep duration in periods following successful mating, while females are unaffected. Single-cell transcriptomics identifies a group of sleep-promoting Rxfp1-expressing neurons in the preoptic area of hypothalamus (POARxfp1 neurons), and fiber photometry reveals selective inhibition of them during and after mating in male mice. Lifting this inhibition via chemogenetic activation reverses sleep suppression in mated males. Monosynaptic retrograde tracing from these POARxfp1 neurons identifies male-biased γ-aminobutyric acid-releasing inputs from the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr). Notably, optogenetic activation of these neurons induces immediate wakefulness specifically in male mice, and BNSTpr → POARxfp1 neurons are hyperactive after mating. Together, these findings establish a BNSTpr → POARxfp1 circuit that integrates reproductive signals for male-specific sleep suppression in mice.