Orexin stimulates breathing via medullary and spinal pathways

• Published in: Journal of applied physiology (1985) Vol. 98; no. 4; pp. 1387 - 1395
• Main Authors: Young, John K, Wu, Mingfei, Manaye, Kebreten F, Kc, Prabha, Allard, Joanne S, Mack, Serdia O, Haxhiu, Musa A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01-04-2005; American Physiological Society
• Subjects: Animals; Arousal - drug effects; Arousal - physiology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - physiology; Intracellular Signaling Peptides and Proteins - administration & dosage; Male; Medulla Oblongata - cytology; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Motor Neurons - cytology; Motor Neurons - drug effects; Motor Neurons - physiology; Neural networks; Neural Pathways - cytology; Neural Pathways - drug effects; Neural Pathways - physiology; Neuropeptides - administration & dosage; Orexin Receptors; Orexins; Phrenic Nerve - cytology; Phrenic Nerve - drug effects; Phrenic Nerve - physiology; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Receptors, Neuropeptide - metabolism; Respiration - drug effects; Respiratory system; Sleep disorders; Spinal Cord - cytology; Spinal Cord - drug effects; Spinal Cord - physiology; Spine; Vertebrates: nervous system and sense organs; phrenic motor neurons; orexin-1 receptors; Central nervous system; Motor neuron; Hypothalamus; pre-Botzinger region; Neuropeptide; Encephalon; Vertebrata; Mammalia; Respiratory control; Respiration; sleep apnea; Orexin; Response stimulus relation
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00914.2004

1 Howard University Specialized Neuroscience Research Program, Departments of Physiology and Anatomy, Washington, District of Columbia, and 2 Departments of Pediatrics and Anatomy, Case Western University, Cleveland, Ohio
Submitted 20 August 2004
; accepted in final form 10 November 2004
A central neuronal network that regulates respiration may include hypothalamic neurons that produce orexin, a peptide that influences sleep and arousal. In these experiments, we investigated 1 ) projections of orexin-containing neurons to the pre-Bötzinger region of the rostral ventrolateral medulla that regulates rhythmic breathing and to phrenic motoneurons that innervate the diaphragm; 2 ) the presence of orexin A receptors in the pre-Bötzinger region and in phrenic motoneurons; and 3 ) physiological effects of orexin administered into the pre-Bötzinger region and phrenic nuclei at the C 3 –C 4 levels. We found orexin-containing fibers within the pre-Bötzinger complex. However, only 0.5% of orexin-containing neurons projected to the pre-Bötzinger region, whereas 2.9% of orexin-containing neurons innervated the phrenic nucleus. Neurons of the pre-Bötzinger region and phrenic nucleus stained for orexin receptors, and activation of orexin receptors by microperfusion of orexin in either site produced a dose-dependent, significant ( P < 0.05) increase in diaphragm electromyographic activity. These data indicate that orexin regulates respiratory activity and may have a role in the pathophysiology of sleep-related respiratory disorders.
hypothalamus; pre-Bötzinger region; phrenic motor neurons; orexin-1 receptors; sleep apnea
Address for reprint requests and other correspondence: J. K. Young, Dept. of Anatomy, Howard Univ. College of Medicine, 520 W St., NW, Washington, DC 20059 (E-mail: jyoung{at}howard.edu )