Endocrine Abstracts

The neural construct underlying the hypothalamic GnRH pulse generator has only recently been identified despite its elegant electrophysiological manifestation (abrupt increases in multiunit electrical activity volleys invariably associated with LH pulses) described over 40 years ago by Ernst Knobil. Following the identification of the arcuate KNDy (Kisspeptin/Neurokinin-B/Dynorphin) neurones as the critical component of the GnRH pulse generator, direct in-vivo calcium imaging of their activity at a population (fibre photometry) and single-cell (gradient-index [GRIN] lens microendoscopy) level has revealed a pattern of episodic synchronisation invariably associated with LH pulses. Although these cutting-edge techniques have greatly advanced our understanding of the GnRH pulse generator, our mathematical modelling highlights that the KNDy neuronal population undergoes sudden qualitative changes in its dynamic behaviour as the basal activity of the population is modulated. In particular, as the basal activity level is increased the system transitions from a silent into a pulsatile mode, while higher levels of basal activity inhibit pulses and reinstate the quiescent state. Crucially, these sudden transitions are a rudimentary characteristic of the mechanisms underlying pulse generation per se. These experimental and modelling techniques will be explored in this presentation.