Fig. 16

Schematic illustrating the connectivity and pleiotropic NOP receptor signaling occurring at VMN SF-1/ARC POMC synapses. N/OFQ activates somatodendritic NOP receptors that activate GIRK channels in SF-1 neurons within the dorsomedial VMN and in POMC neurons within the ARC. This leads to membrane hyperpolarization and a cessation of firing in these two neuronal populations. OFQ can also activate NOP receptors on SF-1 nerve terminals to presynaptically inhibit glutamate release onto ARC POMC neurons. The pleiotropic actions of N/OFQ at VMN SF-1/ARC POMC synapses are greater in males than in females. Moreover, the N/OFQ-induced decrease in glutamate release at SF-1/POMC synapses is accentuated in obese males but not females, whereas the postsynaptic activation of GIRK channels in POMC neurons is heightened in obese females but not males. Regardless of dietary status, these multi-faceted, NOP receptor-mediated effects are attenuated by E₂