Abstract：
:Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARCAgRP neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARCPOMC) neurons are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARCAgRP neurons, ARCPOMC neurons are extremely slow in affecting hunger (many hours). Thus, a temporally analogous, rapid ARC satiety pathway does not exist or is presently unidentified. Here we show that glutamate-releasing ARC neurons expressing oxytocin receptor, unlike ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVHMC4R neurons). Transmission across the ARCGlutamatergic→PVHMC4R synapse is potentiated by the ARCPOMC neuron-derived MC4R agonist, α-melanocyte stimulating hormone (α-MSH). This excitatory ARC→PVH satiety circuit, and its modulation by α-MSH, provides insight into regulation of hunger and satiety.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Fenselau H,Campbell JN,Verstegen AM,Madara JC,Xu J,Shah BP,Resch JM,Yang Z,Mandelblat-Cerf Y,Livneh Y,Lowell BBdoi
10.1038/nn.4442subject
Has Abstractpub_date
2017-01-01 00:00:00pages
42-51issue
1eissn
1097-6256issn
1546-1726pii
nn.4442journal_volume
20pub_type
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