An olfactory bulb GnRH neuronal population translates social relevant odors into reproductive behavior in male mice

Abstract Hypothalamic gonadotropin-releasing hormones (GnRH) neurons are central regulators of fertility and integrate endogenous hormonal status with environmental cues to ensure reproductive success. Here, we found that a novel population of extra-hypothalamic GnRH neurons in the olfactory bulb of adult mice and humans (GnRH OB ) can mediate social recognition. We show that GnRH OB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the hypothalamic median eminence. We demonstrate that male GnRH OB neuronsexpress chemosensory vomeronasal and olfactory receptors, are activated by female odors in vivo, and mediate gonadotropin release in response to female urine. We find that male preference for female odors is enhanced upon chemogenetic activation of GnRH OB neurons, impaired after genetic inhibition or ablation of these cells and relies on GnRH signaling in the posterodorsal medial amygdala. Taken together, these results establish GnRH OB neurons as a central regulatory hub regulating fertility, sex recognition, and mating in males.