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Previous Article | Next Article
The Journal of Neuroscience, December 1, 1998, 18(23):9996-10015
Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems
Christelle Peyron1, Devin K. Tighe1, Anthony N. van den Pol1, 3, Luis de Lecea2, H. Craig Heller1, J. Gregor Sutcliffe2, and Thomas S. Kilduff1 1 Department of Biological Sciences, Stanford University, Stanford, California 94305, 2 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, and 3 Department of Neurosurgery, Yale University, New Haven, Connecticut 06520
The novel neuropeptides called hypocretins (orexins) have recently been identified as being localized exclusively in cell bodies in a subregion of the tuberal part of the hypothalamus. The structure of the hypocretins, their accumulation in vesicles of axon terminals, and their excitatory effect on cultured hypothalamic neurons suggest that the hypocretins function in intercellular communication. To characterize these peptides further and to help understand what physiological functions they may serve, we undertook an immunohistochemical study to examine the distribution of preprohypocretin-immunoreactive neurons and fibers in the rat brain. Preprohypocretin-positive neurons were found in the perifornical nucleus and in the dorsal and lateral hypothalamic areas. These cells were distinct from those that express melanin-concentrating hormone. Although they represent a restricted group of cells, their projections were widely distributed in the brain. We observed labeled fibers throughout the hypothalamus. The densest extrahypothalamic projection was found in the locus coeruleus. Fibers were also seen in the septal nuclei, the bed nucleus of the stria terminalis, the paraventricular and reuniens nuclei of the thalamus, the zona incerta, the subthalamic nucleus, the central gray, the substantia nigra, the raphe nuclei, the parabrachial area, the medullary reticular formation, and the nucleus of the solitary tract. Less prominent projections were found in cortical regions, central and anterior amygdaloid nuclei, and the olfactory bulb. These results suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep-waking cycle.
Key words: neuropeptide; hypothalamus; immunohistochemistry; blood pressure; feeding; autonomic functions; hypocretin; orexin; melanin-concentrating hormone; neuroendocrine
Copyright © 1998 Society for Neuroscience 0270-6474/98/18239996-20$05.00/0
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A. B. Hardy, J. Aioun, C. Baly, K. A. Julliard, M. Caillol, R. Salesse, and P. Duchamp-Viret
Orexin A Modulates Mitral Cell Activity in the Rat Olfactory Bulb: Patch-Clamp Study on Slices and Immunocytochemical Localization of Orexin Receptors
Endocrinology, September 1, 2005; 146(9): 4042 - 4053.
[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]
N. Tsujino, A. Yamanaka, K. Ichiki, Y. Muraki, T. S. Kilduff, K.-i. Yagami, S. Takahashi, K. Goto, and T. Sakurai
Cholecystokinin Activates Orexin/Hypocretin Neurons through the Cholecystokinin A Receptor
J. Neurosci., August 10, 2005; 25(32): 7459 - 7469.
[Abstract] [Full Text] [PDF]
C. M. Kotz, M. A. Mullett, and C. Wang
Diminished feeding responsiveness to orexin A (hypocretin 1) in aged rats is accompanied by decreased neuronal activation
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R359 - R366.
[Abstract] [Full Text] [PDF]
A. J. Thorpe, J. A. Teske, and C. M. Kotz
Orexin A-induced feeding is augmented by caloric challenge
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R367 - R372.
[Abstract] [Full Text] [PDF]
M. G. Lee, O. K. Hassani, and B. E. Jones
Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle
J. Neurosci., July 13, 2005; 25(28): 6716 - 6720.
[Abstract] [Full Text] [PDF]
S. C. Gammie
Current Models and Future Directions for Understanding the Neural Circuitries of Maternal Behaviors in Rodents
Behav Cogn Neurosci Rev, June 1, 2005; 4(2): 119 - 135.
[Abstract] [PDF]
T. Yasuda, T. Masaki, T. Kakuma, M. Hara, T. Nawata, I. Katsuragi, and H. Yoshimatsu
Dual Regulatory Effects of Orexins on Sympathetic Nerve Activity Innervating Brown Adipose Tissue in Rats
Endocrinology, June 1, 2005; 146(6): 2744 - 2748.
[Abstract] [Full Text] [PDF]
S. W. Kok, F. Roelfsema, S. Overeem, G. J. Lammers, M. Frolich, A. E. Meinders, and H. Pijl
Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men
Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E892 - E899.
[Abstract] [Full Text] [PDF]
J. Grivel, V. Cvetkovic, L. Bayer, D. Machard, I. Tobler, M. Muhlethaler, and M. Serafin
The Wake-Promoting Hypocretin/Orexin Neurons Change Their Response to Noradrenaline after Sleep Deprivation
J. Neurosci., April 20, 2005; 25(16): 4127 - 4130.
[Abstract] [Full Text] [PDF]
J. K. Young, M. Wu, K. F. Manaye, P. Kc, J. S. Allard, S. O. Mack, and M. A. Haxhiu
Orexin stimulates breathing via medullary and spinal pathways
J Appl Physiol, April 1, 2005; 98(4): 1387 - 1395.
[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]
Md. N. Alam, S. Kumar, T. Bashir, N. Suntsova, M. M Methippara, R. Szymusiak, and D. McGinty
GABA-mediated control of hypocretin- but not melanin-concentrating hormone-immunoreactive neurones during sleep in rats
J. Physiol., March 1, 2005; 563(2): 569 - 582.
[Abstract] [Full Text] [PDF]
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