In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse

Abstract

Significance Hypothalamic oscillators that generate pulsatile patterns of hormone secretion represent a fundamental physiological feature regulating homeostatic systems. How individual cells within these neural ensembles generate and coordinate episodic activity and resultant pulse secretion is unknown. Recently, arcuate KNDy (kisspeptin/neurokinin B/dynorphin) cells were identified as a critical component of the gonadotrophin-releasing hormone (GnRH) pulse generator required for reproduction. Using in vivo calcium imaging of KNDy neurons in freely moving mice, we reveal that, prior to each GnRH pulse, individual KNDy cells demonstrate synchronized activity with striking temporal order, with subsets of cells behaving as “leaders” or “followers.” Future work to distinguish these novel subpopulations and define mechanisms underlying the temporal ordering of cellular synchronization may provide avenues to regulate pulse secretion.