Hyperexcited limbic neurons represent sexual satiety and reduce mating motivation

Transient sexual experiences can have long-lasting effects on behavioral decisions, but the neural coding that accounts for this change is unclear. We found that the ejaculation experience selectively activated estrogen receptor 2 ( Esr2 )–expressing neurons in the bed nucleus of the stria terminalis (BNST)—BNST Esr2 —and led to persistent decreases in firing threshold for days, during which time the mice displayed sexual satiety. Inhibition of hyperexcited BNST Esr2 elicited fast mating recovery in satiated mice of both sexes. In males, such hyperexcitability reduced mating motivation and was partially mediated by larger HCN (hyperpolarization-activated cyclic nucleotide-gated) currents. Thus, BNST Esr2 not only encode a specific mating action but also represent a persistent state of sexual satiety, and alterations in a neuronal ion channel contribute to sexual experience–dependent long-term changes to mating drive.