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The Journal of Neuroscience, February 14, 2007, 27(7):1529-1533; doi:10.1523/JNEUROSCI.3583-06.2007

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Brief Communications
Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

Xiaosong Ma,¹ Lejla Zubcevic,¹ Jens C. Brüning,² Frances M. Ashcroft,¹ and Denis Burdakov³

¹University Laboratory of Physiology, Oxford OX1 3PT, United Kingdom, ²Institute for Genetics, Department of Mouse Genetics and Metabolism, and Center of Molecular Medicine, University of Cologne, 50674 Köln, Germany, and ³Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom

Correspondence should be addressed to Prof. Frances M. Ashcroft, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. Email: frances.ashroft{at}physiol.ox.ac.uk

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.

Key words: POMC neurons; orexin; hypocretin; appetite; obesity; arcuate nucleus

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Received Aug. 18, 2006; revised Jan. 3, 2007; accepted Jan. 3, 2007.

Correspondence should be addressed to Prof. Frances M. Ashcroft, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. Email: frances.ashroft{at}physiol.ox.ac.uk

This article has been cited by other articles:

				X. Ma, L. Zubcevic, and F. M. Ashcroft Glucose regulates the effects of leptin on hypothalamic POMC neurons PNAS, July 15, 2008; 105(28): 9811 - 9816. [Abstract] [Full Text] [PDF]

				E. Rother, A. C. Konner, and J. C. Bruning Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E810 - E816. [Abstract] [Full Text] [PDF]

				X. Ma, J. Bruning, and F. M. Ashcroft Glucagon-Like Peptide 1 Stimulates Hypothalamic Proopiomelanocortin Neurons J. Neurosci., July 4, 2007; 27(27): 7125 - 7129. [Abstract] [Full Text] [PDF]

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