Figure 12. Proposed model by which activation of Kiss1 neurons governs GnRH neuronal excitability.
High-frequency photostimulation of Kiss1 neurons in the ARH releases NKB that depolarizes and recruits other Kiss1ARH neurons. Dynorphin is co-released and acts presynaptically to modulate (inhibit) the release of NKB. Together the two peptides govern the synchronous activity of Kiss1ARH neurons and promote kisspeptin release that stimulates GnRH release in the median eminence (ME). Kiss1ARH neurons also communicate with the Kiss1AVPV/PeN neurons via the fast neurotransmitter glutamate, which stimulates burst-firing of Kiss1AVPV/PeN neurons. Activation of these rostral Kiss1 neurons releases kisspeptin to robustly excite GnRH neurons via activation of the GPR54 signaling cascade, thereby stimulating the release of GnRH at the time of the preovulatory surge. Kisspeptin, GPR54, NKB, Tacr3 and GnRH are all required for normal fertility.