Credit: B. B. Lowell
Current models for homeostatic control of hunger / satiety lack a rapidly-acting satiety mechanism that is temporally analogous to that provided by rapidly-acting, hunger-promoting ARCAgRP neurons. Our findings report the discovery of this missing component, namely glutamate-releasing oxytocin receptor-expressing neurons in the arcuate nucleus. These neurons converge with ARCAgRP and ARCPOMC neurons on downstream targets and rapidly increase / decrease satiety when experimentally activated / inhibited. Thus, in contrast to the hunger-promoting system where slow- (AgRP) and rapid-acting signals (GABA and NPY) are conveyed by one group of neurons (ARCAgRP neurons), the counteracting satiety-promoting system is split into two parallel-projecting neurons, the previously known ARCPOMC neurons which deliver slow-acting α-MSH, and the previously unknown ARCOxtr neurons which release the rapid-acting transmitter, glutamate. Importantly, these two satiety neurons interact as α-MSH released by ARCPOMC neurons postsynaptically increases glutamatergic transmission across the ARCOxtrPVHMC4R synapse. This missing rapid-acting component, with ARCPOMC neurons, now provides the full “yang” to the ARCAgRP neuron’s “yin”. Our work also provides a mechanism for α-MSH /MC4R regulation of satiety – plasticity of the novel ARCOxtrPVHMC4R synapse.