Female sexual behavior in mice is controlled by kisspeptin neurons

Abstract

Sexual behavior is essential for the survival of many species. In female rodents, mate preference and copulatory behavior depend on pheromones and are synchronized with ovulation to ensure reproductive success. The neural circuits driving this orchestration in the brain have, however, remained elusive. Here, we demonstrate that neurons controlling ovulation in the mammalian brain are at the core of a branching neural circuit governing both mate preference and copulatory behavior. We show that male odors detected in the vomeronasal organ activate kisspeptin neurons in female mice. Classical kisspeptin/Kiss1R signaling subsequently triggers olfactory-driven mate preference. In contrast, copulatory behavior is elicited by kisspeptin neurons in a parallel circuit independent of Kiss1R involving nitric oxide signaling. Consistent with this, we find that kisspeptin neurons impinge onto nitric oxide-synthesizing neurons in the ventromedial hypothalamus. Our data establish kisspeptin neurons as a central regulatory hub orchestrating sexual behavior in the female mouse brain.

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

“…In female rats, male odours lead to activation of AVPV Kiss neurons coincident with elevated LH and increased sexual behaviour [41]. Similarly, in mice, male urine leads to the activation of AVPV Kiss neurons and increased lordosis behaviour in females [42]. These studies in female rodents contrast with our male study, which found that female urine failed to activate AVPV Kiss or ARC Kiss neurons in male mice (online suppl.…”

Sex differences in main olfactory system pathways involved in psychosexual function

“…108,109 Another particularly compelling example involves kisspeptin, a neuropeptide localized mostly in neurons in the hypothalamus that plays a key regulatory role in reproductive physiology. 113 These observations highlight the relationship between Me kisspeptin function and the AOS in rodents. [112][113][114] In the rodent, projections from the AOB, but not the MOB, contact Me kisspeptin neurons, 115 and in female mice, inputs from the AOS, and not the MOS, provide olfactory information to kisspeptin neurons in the periventricular hypothalamus that are essential for female sexual behavior.…”

“…For example, for aromatase, the enzyme that converts testosterone to estradiol, expression is greater in the Me of males than females, and while these neurons appear to be necessary for aggression, they control different forms in males (malemale aggression) and females (maternal aggression). [112][113][114] In the rodent, projections from the AOB, but not the MOB, contact Me kisspeptin neurons, 115 and in female mice, inputs from the AOS, and not the MOS, provide olfactory information to kisspeptin neurons in the periventricular hypothalamus that are essential for female sexual behavior. 110,111 Kisspeptin-synthesizing neurons are also found in the Me, as are neurons that express kisspeptin receptor, and studies have shown that kisspeptin signaling is essential for various aspects of sexual function, including sexual behaviors in both sexes and for olfactory-mediated behaviors.…”

“…110,111 Kisspeptin-synthesizing neurons are also found in the Me, as are neurons that express kisspeptin receptor, and studies have shown that kisspeptin signaling is essential for various aspects of sexual function, including sexual behaviors in both sexes and for olfactory-mediated behaviors. [112][113][114] In the rodent, projections from the AOB, but not the MOB, contact Me kisspeptin neurons, 115 and in female mice, inputs from the AOS, and not the MOS, provide olfactory information to kisspeptin neurons in the periventricular hypothalamus that are essential for female sexual behavior. 113 These observations highlight the relationship between Me kisspeptin function and the AOS in rodents.…”

“…[112][113][114] In the rodent, projections from the AOB, but not the MOB, contact Me kisspeptin neurons, 115 and in female mice, inputs from the AOS, and not the MOS, provide olfactory information to kisspeptin neurons in the periventricular hypothalamus that are essential for female sexual behavior. 113 These observations highlight the relationship between Me kisspeptin function and the AOS in rodents. As for humans, however, recent studies examining brain activation during exposure to sexual-themed images found that systemic administration of kisspeptin enhanced activity in the amygdala as well as anterior and posterior cingulate cortex of heterosexual men, areas often associated with sexual arousal.…”