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Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus (ARC) suppress appetite, and lack of POMC-derived peptides or electrical silencing of POMC neurons causes obesity. ARC POMC neurons are surrounded by nerve terminals containing the wakefulness-promoting peptides orexins/hypocretins, but whether orexin affects their electrical activity has not been tested directly. Here we identify living ARC POMC cells in mouse brain slices by targeted expression of green fluorescent protein. Using whole-cell patch-clamp recordings, we show that orexin suppresses the spontaneous action potential firing of these neurons. Orexin-induced inhibition involves membrane hyperpolarization, a decreased excitatory synaptic drive, and an increased frequency of GABAergic inputs. Our results suggest a reduction in the electrical activity of ARC POMC neurons, which is mediated by changes in presynaptic inputs, contributes to the appetite-enhancing action of orexins.

Original publication




Journal article


J Neurosci

Publication Date





1529 - 1533


2-Amino-5-phosphonovalerate, 6-Cyano-7-nitroquinoxaline-2,3-dione, Animals, Animals, Newborn, Arcuate Nucleus of Hypothalamus, Central Nervous System Stimulants, Drug Interactions, Electric Stimulation, Excitatory Amino Acid Antagonists, Green Fluorescent Proteins, In Vitro Techniques, Intracellular Signaling Peptides and Proteins, Membrane Potentials, Mice, Mice, Transgenic, Neural Inhibition, Neurons, Neuropeptides, Orexins, Patch-Clamp Techniques, Picrotoxin, Pro-Opiomelanocortin, Synaptic Transmission