Abstract
Normal reproductive function and fertility rely on the rhythmic secretion of gonadotropin-releasing hormone (GnRH), which is driven by the hypothalamic GnRH pulse generator. A key regulator of the GnRH pulse generator is the posterodorsal subnucleus of the medial amygdala (MePD), a brain region that is involved in processing external environmental cues, including the effect of stress. However, the neuronal pathways enabling the dynamic, stress-triggered modulation of GnRH secretion remain largely unknown. Here, we employ in silico modelling in order to explore the impact of dynamic inputs on GnRH pulse generator activity. We introduce and analyse a mathematical model representing MePD neuronal circuits composed of GABAergic and glutamatergic neuronal populations, integrating it with our GnRH pulse generator model. Our analysis dissects the influence of excitatory and inhibitory MePD projections' outputs on the GnRH pulse generator's activity and reveals a functionally relevant MePD glutamatergic projection to the GnRH pulse generator, which we probe with in vivo optogenetics. Our study sheds light on how MePD neuronal dynamics affect the GnRH pulse generator activity and offers insights into stress-related dysregulation.