Schematic summarizing the network of neurons and respective neuropeptides thought to participate in the regulation and timing of the female rodent preovulatory LH surge. This working model suggests that several levels of control are upstream of GnRH neurons: hormonal (ovarian-derived E2), circadian (SCN-derived AVP and VIP), and intermediate activators/inhibitors (kisspeptin and RFRP-3). VIP neurons in the SCN project to the DMN and GnRH neurons, and AVP neurons in the SCN project to the DMN and AVPV/PeN Kiss1 neurons, potentially providing circadian information relevant to the timing of the LH surge. Kiss1 neurons directly stimulate GnRH neurons, while RFRP-3 neurons directly inhibit them. Some RFRP-3 neurons also project to the AVPV region, but it is not known if these projections target Kiss1 neurons. GnRH neurons integrate input from Kiss1, RFRP-3, and VIP neurons directly and may respond to some of these signals in a temporally-gated manner. In addition, GnRH neurons may possess endogenous circadian oscillators, the function of which is unknown. See text for more detailed description and explanation of abbreviations.
Key: Solid lines with boutons represent neuronal connections, dotted lines with arrowhead represent hormonal pathways; Solid sinusoid and dotted sinusoid represents cell-autonomous oscillatory activity and potential cell-autonomous oscillatory activity, respectively.