Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice

Reproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalamic arcuate nucleus (ARC(kiss)), the pulse generator of GnRH. The pulsatility of GnRH release, as assessed by the amount of circulating gonadotropin, is markedly reduced in aged animals, suggesting that the malfunctions of ARC(kiss) may be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARC(kiss) during the natural transition to reproductive senescence remain unclear. Herein, we introduce chronic in vivo Ca(2+) imaging of ARC(kiss) in female mice by fiber photometry to monitor the synchronous episodes of ARC(kiss) (SEs(kiss)), a known hallmark of GnRH pulse generator activity, from the fully reproductive to acyclic phase over 1 year. During the reproductive phase, we find that not only the frequency, but also the intensities and waveforms of individual SEs(kiss), vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEs(kiss) patterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARC(kiss) activities in aging female mice. More generally, our findings demonstrate the utility of fiber-photometry-based chronic imaging of neuroendocrine regulators in the brain to characterize aging-associated malfunction.