Shifting GnRH Neuron Ensembles Underlie Successive Preovulatory Luteinizing Hormone Surges

The gonadotropin-releasing hormone (GnRH) neurons operate as a neuronal ensemble exhibiting coordinated activity once every reproductive cycle to generate the preovulatory GnRH surge. Using GCaMP fiber photometry at the GnRH neuron distal dendrons to measure the output of this widely scattered population in female mice, we find that the onset, amplitude, and profile of GnRH neuron surge activity exhibits substantial variability from cycle to cycle both between and within individual mice. This was also evident when measuring successive proestrous luteinizing hormone surges. Studies combining short (c-Fos and c-Jun) and long (genetic robust activity marking) term indices of immediate early gene activation revealed that, while ∼50% of GnRH neurons were activated at the time of each surge, only half of these neurons had been active during the previous proestrous surge. These observations reveal marked inter- and intra-individual variability in the GnRH surge mechanism. Remarkably, different subpopulations of overlapping GnRH neurons are recruited to the ensemble each estrous cycle to generate the GnRH surge. While engendering variability in the surge mechanism itself, this likely provides substantial robustness to a key event underlying mammalian reproduction.