Abstract
Pheromones play a crucial role to identify potential mates and sexual motivation in mice. These molecules are detected by a specialized circuit which initiates in the nasal septum and then relies on GnRH neurons in the hypothalamus in a sex-dependent manner. Female pheromones induce LH/testosterone release in male mice whereas male pheromones induce LH release in female mice. Kisspeptin is a potent stimulator of GnRH release. Its expression is sexually dimorphic in the hypothalamus, and it is the relay of the negative feedback of sexual steroids on GnRH neurons. In addition, the same group recently showed that a specific population of Kisspeptin neurons located in the anterior part of the hypothalamus of female mice are activated by male pheromones. These neurons were therefore natural candidates as a hub to control both sexual behavior and ovulation.
Highlights
Sexual behavior is essential for the survival of many species
We recently found that the RP3V kisspeptin neuronal population in female mice is activated by male but not by female pheromones[19], raising the possibility that these neurons serve reproductive functions in addition to providing estradiol feedback to gonadotropinreleasing hormone (GnRH) neurons
To determine the olfactory input pathway impinging onto these cells, we selectively ablated the vomeronasal organ (VNO) by surgical removal and/or the main olfactory epithelium (MOE) by intranasal infusion with a zinc sulfate (ZnSO4) solution in female C57Bl/6J mice
Summary
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. We recently found that the RP3V kisspeptin neuronal population in female mice is activated by male but not by female pheromones[19], raising the possibility that these neurons serve reproductive functions in addition to providing estradiol feedback to GnRH neurons. We demonstrate that the RP3V kisspeptin neuronal population is necessary for the expression of both male-directed mate preference and lordosis behavior using specific viral-based cell ablation techniques and optogenetic stimulation. We analyzed the neural circuitry downstream of RP3V kisspeptin neurons and found that mutant mice lacking GnRH secretion in adulthood failed to show any male-directed preference. These data suggest that kisspeptin neurons act through GnRH neurons to trigger olfactory-driven mate preferences in female mice. Our results demonstrate that kisspeptin governs both mate preference and sexual motivation in female mice, indicating that sexual behavior and ovulation are coordinated by the same neuropeptide
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