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The neuropeptides orexins/hypocretins are essential for normal wakefulness and energy balance, and disruption of their function causes narcolepsy and obesity. Although much is known of the role of orexins in sleep/wake behavior, it remains unclear how they stimulate feeding and metabolism. One of the main targets of orexinergic neurons is the arcuate nucleus (ARC) of the hypothalamus, which plays a key role in feeding and energy homeostasis. By combining patch-clamp and RT-multiplex PCR analysis of individual neurons in mouse brain slices, we show that an electrophysiologically distinct subset of ARC neurons coexpress orexin receptors and glutamate decarboxylase-67 and are excited by orexin. Acting on postsynaptic orexin type 2 receptors, orexin activates a sodium-calcium exchange current, thereby depolarizing the cell and increasing its firing frequency. Because GABA is a potent stimulus for feeding, in both the ARC and its main projection site, these results suggest a mechanism for how orexin may control appetite.


Journal article


J Neurosci

Publication Date





4951 - 4957


Animals, Arcuate Nucleus of Hypothalamus, Calcium, Carrier Proteins, Chelating Agents, Egtazic Acid, Electrophysiology, Energy Metabolism, Glutamate Decarboxylase, In Vitro Techniques, Intracellular Signaling Peptides and Proteins, Isoenzymes, Male, Mice, Mice, Inbred C57BL, Neurons, Neuropeptides, Orexin Receptors, Orexins, Patch-Clamp Techniques, Polymerase Chain Reaction, Receptors, G-Protein-Coupled, Receptors, Neuropeptide, Sodium-Calcium Exchanger, gamma-Aminobutyric Acid