QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 15, 2003, 23(12):4951-4957

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (37) Citing Articles via Google Scholar Google Scholar Articles by Burdakov, D. Articles by Ashcroft, F. M. Search for Related Content PubMed PubMed Citation Articles by Burdakov, D. Articles by Ashcroft, F. M.

 Previous Article  |  Next Article 

Orexin Excites GABAergic Neurons of the Arcuate Nucleus by Activating the Sodium—Calcium Exchanger

Denis Burdakov, ^* Birgit Liss, ^* and Frances M. Ashcroft

University Laboratory of Physiology, Oxford, OX1 3PT, United Kingdom

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.

Key words: orexin; hypocretin; arcuate nucleus; sleep; feeding; energy balance; neuropeptides; hypothalamus

---

Received Dec. 26, 2002; revised Mar. 4, 2003; accepted Mar. 9, 2003.

This article has been cited by other articles:

				X. Ma, L. Zubcevic, J. C. Bruning, F. M. Ashcroft, and D. Burdakov Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin J. Neurosci., February 14, 2007; 27(7): 1529 - 1533. [Abstract] [Full Text] [PDF]

				J. Nasman, G. Bart, K. Larsson, L. Louhivuori, H. Peltonen, and K. E. O. Akerman The Orexin OX1 Receptor Regulates Ca2+ Entry via Diacylglycerol-Activated Channels in Differentiated Neuroblastoma Cells. J. Neurosci., October 18, 2006; 26(42): 10658 - 10666. [Abstract] [Full Text] [PDF]

				H. Huang, P. Ghosh, and A. N. van den Pol Prefrontal Cortex-Projecting Glutamatergic Thalamic Paraventricular Nucleus-Excited by Hypocretin: A Feedforward Circuit That May Enhance Cognitive Arousal J Neurophysiol, March 1, 2006; 95(3): 1656 - 1668. [Abstract] [Full Text] [PDF]

				S.-i. Sekizawa and A. C. Bonham Group I Metabotropic Glutamate Receptors on Second-Order Baroreceptor Neurons Are Tonically Activated and Induce a Na+-Ca2+ Exchange Current J Neurophysiol, February 1, 2006; 95(2): 882 - 892. [Abstract] [Full Text] [PDF]

				O. Dergacheva, X. Wang, Z.-G. Huang, E. Bouairi, C. Stephens, C. Gorini, and D. Mendelowitz Hypocretin-1 (Orexin-A) Facilitates Inhibitory and Diminishes Excitatory Synaptic Pathways to Cardiac Vagal Neurons in the Nucleus Ambiguus J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1322 - 1327. [Abstract] [Full Text] [PDF]

				C. Acuna-Goycolea, N. Tamamaki, Y. Yanagawa, K. Obata, and A. N. van den Pol Mechanisms of Neuropeptide Y, Peptide YY, and Pancreatic Polypeptide Inhibition of Identified Green Fluorescent Protein-Expressing GABA Neurons in the Hypothalamic Neuroendocrine Arcuate Nucleus J. Neurosci., August 10, 2005; 25(32): 7406 - 7419. [Abstract] [Full Text] [PDF]

				D. Burdakov, O. Gerasimenko, and A. Verkhratsky Physiological Changes in Glucose Differentially Modulate the Excitability of Hypothalamic Melanin-Concentrating Hormone and Orexin Neurons In Situ J. Neurosci., March 2, 2005; 25(9): 2429 - 2433. [Abstract] [Full Text] [PDF]

				Q. V. Hoang, P. Zhao, S. Nakajima, and Y. Nakajima Orexin (Hypocretin) Effects on Constitutively Active Inward Rectifier K+ Channels in Cultured Nucleus Basalis Neurons J Neurophysiol, December 1, 2004; 92(6): 3183 - 3191. [Abstract] [Full Text] [PDF]

				X. Fioramonti, A. Lorsignol, A. Taupignon, and L. Penicaud A New ATP-Sensitive K+ Channel-Independent Mechanism Is Involved in Glucose-Excited Neurons of Mouse Arcuate Nucleus Diabetes, November 1, 2004; 53(11): 2767 - 2775. [Abstract] [Full Text] [PDF]

				D. Burdakov Electrical Signaling in Central Orexin/Hypocretin Circuits: Tuning Arousal and Appetite to Fit the Environment Neuroscientist, August 1, 2004; 10(4): 286 - 291. [Abstract] [PDF]

				K. A. Kohlmeier, T. Inoue, and C. S. Leonard Hypocretin/Orexin Peptide Signaling in the Ascending Arousal System: Elevation of Intracellular Calcium in the Mouse Dorsal Raphe and Laterodorsal Tegmentum J Neurophysiol, July 1, 2004; 92(1): 221 - 235. [Abstract] [Full Text] [PDF]

				M. Wu, L. Zaborszky, T. Hajszan, A. N. van den Pol, and M. Alreja Hypocretin/Orexin Innervation and Excitation of Identified Septohippocampal Cholinergic Neurons J. Neurosci., April 7, 2004; 24(14): 3527 - 3536. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help