Kisspeptin, a recently-identified neuropeptide encoded by the Kiss1 gene, is both necessary and sufficient for puberty onset and adulthood fertility; however, exactly how Kiss1 neurons, which are known to be located in the hypothalamus, are themselves regulated is poorly understood. In females, Kiss1 neurons in the anterior hypothalamus are regulated by temporal signals from the brain?s circadian clock, thereby generating a precisely-timed activation of the reproductive axis that results in ovulation. Interestingly, this circadian regulation of Kiss1 neurons is fully dependent on the presence of the hormone estradiol, but how and where in the brain estradiol acts to induce the circadian activation of Kiss1 neurons is unknown. Additionally, the Kauffman lab has identified a novel extra-hypothalamic population of Kiss1 neurons in the amygdala which is also stimulated by estradiol; however, the molecular mechanisms of this regulation and the functions of amygdala Kiss1 neurons are completely unknown. Using mice, this research will ascertain the neuroanatomical location and molecular mechanism(s) by which hypothalamic Kiss1 neurons are regulated by both hormonal signals and circadian cues, and will also elucidate the hormonal regulatory mechanisms and potential functions of the novel Kiss1 population located in the amygdala. This intellectual merit of this research is a better understanding of how, when, and where in the brain hormones, particularly estradiol, regulate the function of critical pubertal and reproductive neural circuits, in particular, Kiss1 circuits. The research component is complimented and integrated with the outreach and broader impact aspects, which are to directly train and educate undergraduate and graduate students in hands-on biology research, to participate in the UCSD Initiative for Maximizing Student Diversity which engages and mentors undergraduate minority students in biology research, and to design and manage a new dynamic science website (Neuroendo Now) that serves as a public forum for, and disseminates current information pertaining to advances in neuroendocrinology.
