Abstract

Journal of Comparative NeurologyVolume 415, Issue 2 p. 145-159 Rapid Publication Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system Tamas L. Horvath, Corresponding Author Tamas L. Horvath tamas.horvath@yale.edu Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520Department of Obstetrics and Gynecology, Yale Medical School, 333 Cedar St. FMB 339, New Haven CT 06520.Search for more papers by this authorChristelle Peyron, Christelle Peyron Department of Biological Sciences, Stanford University, Stanford, California 94305Search for more papers by this authorSabrina Diano, Sabrina Diano Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520Search for more papers by this authorAlexander Ivanov, Alexander Ivanov Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Search for more papers by this authorGary Aston-Jones, Gary Aston-Jones Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Search for more papers by this authorThomas S. Kilduff, Thomas S. Kilduff Department of Biological Sciences, Stanford University, Stanford, California 94305Search for more papers by this authorAnthony N. van den Pol, Anthony N. van den Pol Department of Biological Sciences, Stanford University, Stanford, California 94305 Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520Search for more papers by this author Tamas L. Horvath, Corresponding Author Tamas L. Horvath tamas.horvath@yale.edu Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520Department of Obstetrics and Gynecology, Yale Medical School, 333 Cedar St. FMB 339, New Haven CT 06520.Search for more papers by this authorChristelle Peyron, Christelle Peyron Department of Biological Sciences, Stanford University, Stanford, California 94305Search for more papers by this authorSabrina Diano, Sabrina Diano Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520Search for more papers by this authorAlexander Ivanov, Alexander Ivanov Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Search for more papers by this authorGary Aston-Jones, Gary Aston-Jones Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104Search for more papers by this authorThomas S. Kilduff, Thomas S. Kilduff Department of Biological Sciences, Stanford University, Stanford, California 94305Search for more papers by this authorAnthony N. van den Pol, Anthony N. van den Pol Department of Biological Sciences, Stanford University, Stanford, California 94305 Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520Search for more papers by this author First published: 01 November 1999 https://doi.org/10.1002/(SICI)1096-9861(19991213)415:23.0.CO;2-2Citations: 385AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Hypocretin has been identified as a regulator of metabolic and endocrine systems. Several brain regions involved in the central regulation of autonomic and endocrine processes or attention are targets of extensive hypocretin projections. The most dense arborization of hypocretin axons in the brainstem was detected in the locus coeruleus (LC). Multiple labeling immunocytochemistry revealed a massive synaptic innervation of catecholaminergic LC cells by hypocretin axon terminals in rats and monkeys. In both species, all tyrosine hydroxylase-immunopositive cells in the LC examined by electron microscopy were found to receive asymmetrical (excitatory) synaptic contacts from multiple axons containing hypocretin. In parallel electrophysiological studies with slices of rat brain, all LC cells showed excitatory responses to the hypocretin-2 peptide. Hypocretin-2 uniformly increased the frequency of action potentials in these cells, even in the presence of tetrodotoxin, indicating that receptors responding to hypocretin were expressed in LC neurons. Two mechanisms for the increased firing rate appeared to be a reduction in the slow component of the afterhyperpolarization (AHP) and a modest depolarization. Catecholamine systems in other parts of the brain, including those found in the medulla, zona incerta, substantia nigra or olfactory bulb, received significantly less hypocretin input. Comparative analysis of lateral hypothalamic input to the LC revealed that hypocretin-containing axon terminals were substantially more abundant than those containing melanin-concentrating hormone. The present results provide evidence for direct action of hypothalamic hypocretin cells on the LC noradrenergic system in rats and monkeys. Our observations suggest a signaling pathway via which signals acting on the lateral hypothalamus may influence the activity of the LC and thereby a variety of CNSfunctions related to noradrenergic innervation, including vigilance, attention, learning, and memory. Thus, the hypocretin innervation of the LC may serve to focus cognitive processes to compliment hypocretin-mediated activation of autonomic centers already described. J. Comp. Neurol. 415:145–159, 1999. © 1999 Wiley-Liss, Inc. Citing Literature Volume415, Issue213 December 1999Pages 145-159 RelatedInformation