Figure 8.

Model for integration of circadian and estradiol signals in RP3V kisspeptin neurons. SCN AVP neurons project to RP3V kisspeptin neurons, providing time of day-related cues (daily signal) to these neurons. In ovariectomized (OVX) mice (left), AVP has minimal effects on RP3V kisspeptin neuron firing. In intact females, circulating estradiol has a permissive effect in enabling AVP signaling to alter firing in RP3V kisspeptin neurons. This remains constant across the estrous cycle (red arrow, middle and right). Elevated proestrous estradiol levels or high estrogen treatment of ovariectomized mice (black arrows) upregulates kiss1 gene expression and specific ion currents (e.g., I_h and the I_T), and may promote yet-to-be identified effects on RP3V kisspeptin neuron function (other?). These downstream estradiol-dependent alterations likely enable efficient integration of the SCN AVP input to enhance the final output of RP3V kisspeptin cells to GnRH neurons at the time of the LH surge (right).