A unified survival theory of the functioning of the hypocretinergic system

Journal of Applied Physiology

Volumn 115, Issue 7, 2013, Pages 954-971

  Chase, Michael H ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Behaviors; Hypocretin; Orexin; Survival

Indexed keywords

NEUROPEPTIDE; OREXIN; OREXINS; SIGNAL PEPTIDE;

ANIMAL; BEHAVIORS; HUMAN; HYPOTHALAMUS; METABOLISM; NERVE CELL; PHYSIOLOGY; REVIEW; SURVIVAL;

BEHAVIORS; HYPOCRETIN; OREXIN; SURVIVAL;

ANIMALS; HUMANS; HYPOTHALAMUS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; NEURONS; NEUROPEPTIDES; SURVIVAL;

EID: 84885213018     PISSN: 87507587     EISSN: 15221601     Source Type: Journal    
DOI: 10.1152/japplphysiol.00700.2012     Document Type: Review

References (197)

1. Akhtari M, Bragin A, Cohen M, Moats R, Brenker F, Lynch MD, Vinters HV, Engel J, Jr. Functionalized magnetonanoparticles for MRI diagnosis and localization in epilepsy. Epilepsia 49: 1419-1430, 2008.
2. Akhtari M, Engel J. Patents PCT/US06/10334, EU06739214.2. 2006.
3. Alberts JR, Friedman MI. Olfactory bulb removal but not anosmia increases emotionality and mouse killing. Nature 238: 454-455, 1972.
4. Alvarez CE, Sutcliffe JG. Hypocretin is an early member of the incretin gene family. Neurosci Lett 324: 169-172, 2002.
5. Anand BK, Brobeck Jr. Localization of a "feeding center" in the hypothalamus of the rat. Proc Soc Exp Biol Med 77: 323-324, 1951.
6. Anand BK, Chhina GS, Sharman KN, Dua S, Singh B. Activity of single neurons in the hypothalamic feeding centers: effect of glucose. Am J Physiol 207: 1146-1154, 1964.
7. Apelbaum AF, Perrut A, Chaput M. Hypocretin A effects on the olfactory bulb spontaneous activity and odor responsiveness in freely breathing rats. Regul Pept 129: 49-61, 2005.
8. Aran A, Shors I, Lin L, Mignot E, Schimmel MS. CSF levels of hypocretin-1 (orexin-A) peak during early infancy in humans. Sleep 35: 187-191, 2012.
9. Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, Richardson KA. Lateral hypothalamic orexin/hypocretin neurons: a role in reward-seeking and addiction. Brain Res 1314: 74-90, 2010.
10. Baier PC, Weinhold SL, Huth V, Gottwald B, Ferstl R, Hinze-Selch D. Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1). Brain 131: 2734-2741, 2008.
11. Baumann CR. Traumatic brain injury and disturbed sleep and wakefulness. Neuromolecul Med In press.
12. Bayer L, Serafin M, Eggermann E, Saint-Mleux B, Machard D, Jones BE, Muhlethaler M. Exclusive postsynaptic action of hypocretinorexin on sublayer 6b cortical neurons. J Neurosci 24: 6760-6764, 2004.
13. Beiras-Fernandez A, Gallego R, Blanco M, Garcia-Caballero T, Dieguez C, Beiras A. Merkel cells, a new localization of prepro-orexin and orexin receptors. J Anat 204: 117-122, 2004.
14. Benoit SC, Tracy AL, Davis JF, Choi D, Clegg DJ. Novel functions of orexigenic hypothalamic peptides: from genes to behavior. Nutrition 24: 843-847, 2008.
15. Berridge CW, Schmeichel BE, Espana RA. Noradrenergic modulation of wakefulness/arousal. Sleep Med Rev 16: 187-197, 2012.
16. Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42: 33-84, 2003.
17. Berthoud HR, Munzberg H. The lateral hypothalamus as integrator of metabolic and environmental needs: from electrical self-stimulation to opto-genetics. Physiol Behav 104: 29-39, 2011.
18. Berthoud HR, Patterson LM, Sutton GM, Morrison C, Zheng H. Orexin inputs to caudal raphe neurons involved in thermal, cardiovascular, and gastrointestinal regulation. Histochem Cell Biol 123: 147-156, 2005.
19. Bingham S, Davey PT, Babbs AJ, Irving EA, Sammons MJ, Wyles M, Jeffrey P, Cutler L, Riba I, Johns A, Porter RA, Upton N, Hunter AJ, Parsons AA. Orexin-A, an hypothalamic peptide with analgesic properties. Pain 92: 81-90, 2001.
20. Boschen KE, Fadel J, Burk JA. Effects of systemic and intra-basalis blockade of orexin-1 receptors on attentional performance in rats (Abstract). Soc Neurosci Abstracts 387.315/SS362, 2008.
21. Bouret S, Richmond BJ. Relation of locus coeruleus neurons in monkeys to Pavlovian and operant behaviors. J Neurophysiol 101: 898-911, 2009.
22. Bourgin P, Zeitzer JM, Mignot E. CSF hypocretin-1 assessment in sleep and neurological disorders. Lancet Neurol 7: 649-662, 2008.
23. Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, coma. N Engl J Med 363: 2638-2650, 2010.
24. Brudzynski SM, Holland G. Acoustic characteristics of air puff-induced 22-kHz alarm calls in direct recordings. Neurosci Biobehav Rev 29: 1169-1180, 2005.
25. Brzozowski T, Konturek PC, Sliwowski Z, Drozdowicz D, Burnat G, Pajdo R, Pawlik M, Bielanski W, Kato I, Kuwahara A, Konturek SJ, Pawlik WW. Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglandins, sensory afferent neuropeptides and nitric oxide. Regul Pept 148: 6-20, 2008.
26. Buonomano DV, Merzenich MM. Cortical plasticity: from synapses to maps. Annu Rev Neurosci 21: 149-186, 1998.
27. Canteras NS. The medial hypothalamic defensive system: hodological organization and functional implications. Pharmacol Biochem Behav 71: 481-491, 2002.
28. Canteras NS, Chiavegatto S, Ribeiro do Valle LE, Swanson LW. Severe reduction of rat defensive behavior to a predator by discrete hypothalamic chemical lesions. Brain Res Bull 44: 297-305, 1997.
29. Canteras NS, Mota-Ortiz SR, Motta SC. What ethologically based models have taught us about the neural systems underlying fear and anxiety. Braz J Med Biol Res 45: 321-327, 2012.
30. Carter ME, Brill J, Bonnavion P, Huguenard JR, Huerta R, de Lecea L. Mechanism for hypocretin-mediated sleep-to-wake transitions. Proc Natl Acad Sci USA 109: 2635-2644, 2012.
31. Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF. Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci 28: 12107-12119, 2008.
32. Chase MH. Motor control during sleep and wakefulness: clarifying controversies and resolving paradoxes. Sleep Med Rev 17: 299-312, 2013.
33. Chase MH, Babb M. Masseteric reflex response to reticular stimulation reverses during active sleep compared with wakefulness or quiet sleep. Brain Res 59: 421-426, 1973.
34. Chase MH, Monoson R, Watanabe K, Babb MI. Somatic reflex response-reversal of reticular origin. Exp Neurol 50: 561-567, 1976.
35. Chen CT, Dun SL, Kwok EH, Dun NJ, Chang JK. Orexin A-like immunoreactivity in the rat brain. Neurosci Lett 260: 161-164, 1999.
36. Choi DL, Davis JF, Fitzgerald ME, Benoit SC. The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats. Neuroscience 167: 11-20, 2010.
37. Clemente CD, Chase MH. Neurological substrates of aggressive behavior. Annu Rev Physiol 35: 329-356, 1973.
38. Comoli E, Ribeiro-Barbosa ER, Canteras NS. Predatory hunting and exposure to a live predator induce opposite patterns of FOS immunoreactivity in the PAG. Behav Brain Res 138: 17-28, 2003.
39. Cramer SC, Sur M, Dobkin BH, O'Brien C, Sanger TD, Trojanowski JQ, Rumsey JM, Hicks R, Cameron J, Chen D, Chen WG, Cohen LG, deCharms C, Duffy CJ, Eden GF, Fetz EE, Filart R, Freund M, Grant SJ, Haber S, Kalivas PW, Kolb B, Kramer AF, Lynch M, Mayberg HS, McQuillen PS, Nitkin R, Pascual-Leone A, Reuter-Lorenz P, Schiff N, Sharma A, Shekim L, Stryker M, Sullivan EV, Vinogradov S. Harnessing neuroplasticity for clinical applications. Brain 134: 1591-1609.
40. Dahmen N, Kasten M, Mittag K, Muller MJ. Narcoleptic and schizophrenic hallucinations. Implications for differential diagnosis and pathophysiology. Eur J Health Econ 3, Suppl 2: S94-S98, 2002.
41. Dauvilliers Y, Rompré S, Gagnon JF, Vendette M, Petit D, Montplaisir J. REM sleep characteristics in narcolepsy and REM sleep behavior disorder. Sleep 30: 844-849, 2007.
42. Davis SF, Williams KW, Xu W, Glatzer NR, Smith BN. Selective enhancement of synaptic inhibition by hypocretin (orexin) in rat vagal motor neurons: implications for autonomic regulation. J Neurosci 23: 3844-3854, 2003.
43. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS 2nd, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95: 322-327, 1998.
44. de Lecea L, Sutcliffe JG. The hypocretins and sleep. FEBS J 272: 5675-5688, 2005.
45. de Lecea L, Sutcliffe JG. Hypocretins: Integrators of Physiological Functions. New York, NY: Springer, 2005.
46. de Oliveira CV, Rosas-Arellano MP, Solano-Flores LP, Ciriello J. Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 284: H1369-H1377, 2003.
47. De Oliveira DB, de Almeida AP, De BASGL, Auvin C, Kaiser CR, Costa SS. First isolation of a symmetrical glycosylated methylene bisflavonoid. Planta Med 69: 382-384, 2003.
48. Demanez JP, Demanez L. Anatomophysiology of the central auditory nervous system: basic concepts. Acta Otorhinolaryngol Belg 57: 227-236, 2003.
49. Dominguez L, Morona R, Joven A, Gonzalez A, Lopez JM. Immunohistochemical localization of orexins (hypocretins) in the brain of reptiles and its relation to monoaminergic systems. J Chem Neuroanat 39: 20-34, 2010.
50. Eagleman DM. Human time perception and its illusions. Curr Opin Neurobiol 18: 131-136, 2008.
51. Edwards DH, Heitler WJ, Krasne FB. Fifty years of a command neuron: the neurobiology of escape behavior in the crayfish. Trends Neurosci 22: 153-161, 1999.
52. Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, Saper CB, Scammell TE. Fos expression in orexin neurons varies with behavioral state. J Neurosci 21: 1656-1662, 2001.
53. Fukushima K, Wells SG, Yamanobe T, Takeichi N, Shinmei Y, Fukushima J. Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys. Exp Brain Res 139: 473-481, 2001.
54. Fung SJ, Xi MC, Zhang JH, Yamuy J, Sampogna S, Tsai KL, Lim V, Morales FR, Chase MH. Eszopiclone prevents excitotoxicity and neurodegeneration in the hippocampus induced by experimental apnea. Sleep 32: 1593-1601, 2009.
55. Furigo IC, de Oliveira WF, de Oliveirs AR, Comoli E, Baldo MV, Mota-Ortiz SR, Canteras NS. The role of the superior colliculus in predatory hinting. Neuroscience 165: 1-15, 2010.
56. Furlong TM, Vianna DM, Liu L, Carrive P. Hypocretin/orexin contributes to the expression of some but not all forms of stress and arousal. Eur J Neurosci 30: 1603-1614, 2009.
57. Gao Q, Horvath TL. Neuronal control of energy homeostasis. FEBS Lett 582: 132-141, 2008.
58. Gascuel J, Lemoine A, Rigault C, Datiche F, Benani A, Penicaud L, Lopez-Mascaraque L. Hypothalamus-olfactory system crosstalk: orexin a immunostaining in mice (Abstract). Front Neuroanat 6: 44, 2012.
59. Gould E, Reeves AJ, Graziano MS, Gross CG. Neurogenesis in the neocortex of adult primates. Science 286: 548-552, 1999.
60. Grimaldi D, Agati P, Pierangeli G, Franceschini C, Guaraldi P, Barletta G, Vandi S, Cevoli S, Plazzi G, Montagna P, Cortelli P. Hypocretin deficiency in narcolepsy with cataplexy is associated with a normal body core temperature modulation. Chronobiol Int 27: 1596-1608, 2010.
61. Grimaldi D, Calandra-Buonaura G, Provini F, Agati P, Pierangeli G, Franceschini C, Barletta G, Plazzi G, Montagna P, Cortelli P. Abnormal sleep-cardiovascular system interaction in narcolepsy with cataplexy: effects of hypocretin deficiency in humans. Sleep 35: 519-528, 2012.
62. Grivel J, Cvetkovic V, Bayer L, Machard D, Tobler I, Muhlethaler M, Serafin M. The wake-promoting hypocretin/orexin neurons change their response to noradrenaline after sleep deprivation. J Neurosci 25: 4127-4130, 2005.
63. Hagan JJ, Leslie RA, Patel S. Orexin A activates locus coeruleus cell firing and increases arousal in the rat (Abstract). Proc Natl Acad Sci USA 96: 10911, 1999.
64. Hardy AB, Aioun J, Baly C, Julliard KA, Caillol M, Salesse R, Duchamp-Viret P. Orexin A modulates mitral cell activity in the rat olfactory bulb: patch-clamp study on slices and immunocytochemical localization of orexin receptors. Endocrinology 146: 4042-4053, 2005.
65. Heinonen MV, Purhonen AK, Makela KA, Herzig KH. Functions of orexins in peripheral tissues. Acta Physiol (Oxf) 192: 471-485, 2008.
66. Hervieu GJ, Cluderay JE, Harrison DC, Roberts JC, Leslie RA. Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience 103: 777-797, 2001.
67. Hess R. The electroencephalogram in sleep. Electroencephalogr Clin Neurophysiol 16: 44-55, 1964.
68. Hirota K, Kushikata T, Kudo M, Kudo T, Lambert DG, Matsuki A. Orexin A and B evoke noradrenaline release from rat cerebrocortical slices. Br J Pharmacol 134: 1461-1466, 2001.
69. Holland PC, Angeli N, Lassetter H, Wheeler DS. Unilateral lesions of lateral hypothalamic orexin neurons impair surprise-induced enhancements of learning. Soc Neurosci Program 387.16/SS63: 2008.
70. Holstege G. The emotional motor system. Eur J Morphol 30: 67-79, 1992.
71. Horvath TL, Gao XB. Input organization and plasticity of hypocretin neurons: possible clues to obesity's association with insomnia. Cell Metab 1: 279-286, 2005.
72. Horvath TL, Peyron C, Diano S, Ivanov A, Aston-Jones G, Kilduff TS, van Den Pol AN. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J Comp Neurol 415: 145-159, 1999.
73. Ida T, Nakahara K, Katayama T, Murakami N, Nakazato M. Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats. Brain Res 821: 526-529, 1999.
74. Ito N, Yabe T, Gamo Y, Nagai T, Oikawa T, Yamada H, Hanawa TI. Administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation. Neuroscience 157: 720-732, 2008.
75. Jacques S. Brain stimulation and reward: "pleasure centers" after twentyfive years. Neurosurgery 5: 277-283, 1979.
76. Johnson PL, Samuels BC, Fitz SD, Federici LM, Hammes N, Early MC, Truitt W, Lowry CA, Shekhar A. Orexin 1 receptors are a novel target to modulate panic responses and the panic brain network. Physiol Behav In press.
77. Johren O, Bruggemann N, Dominiak P. Orexins (hypocretins) and adrenal function. Horm Metab Res 36: 370-375, 2004.
78. Johren O, Neidert SJ, Kummer M, Dendorfer A, Dominiak P. Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology 142: 3324-3331, 2001.
79. Jones BE. Modulation of cortical activation and behavioral arousal by cholinergic and orexinergic systems. Ann NY Acad Sci 1129: 26-34, 2008.
80. Julliard AK, Chaput MA, Apelbaum A, Aime P, Mahfouz M, Duchamp-Viret P. Changes in rat olfactory detection performance induced by orexin and leptin mimicking fasting and satiation. Behav Brain Res 183: 123-129, 2007.
81. Kagerer SM, Johren O. Interactions of orexins/hypocretins with adrenocortical functions. Acta Physiol (Oxf) 198: 361-371, 2010.
82. Kayaba Y, Nakamura A, Kasuya Y, Ohuchi T, Yanagisawa M, Komuro I, Fukuda Y, Kuwaki T. Attenuated defense response and low basal blood pressure in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol 285: R581-R593, 2003.
83. Kim MK, Park HJ, Kim SR, Choi YK, Shin HK, Jeon JH, Jang HO, Yun I, Bae SK, Bae MK. Angiogenic role of orexin-A via the activation of extracellular signal-regulated kinase in endothelial cells. Biochem Biophys Res Commun 403: 59-65, 2010.
84. Kirchgessner AL, Liu M. Orexin synthesis and response in the gut. Neuron 24: 941-951, 1999.
85. Kohlmeier KA, Lopez-Rodriguez F, Liu RH, Morales FR, Chase MH. State-dependent phenomena in cat masseter motoneurons. Brain Res 722: 30-38, 1996.
86. Korotkova TM, Brown RE, Sergeeva OA, Ponomarenko AA, Haas HL. Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat. Eur J Neurosci 23: 2677-2685, 2006.
87. Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE. Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci 23: 7-11, 2003.
88. Krout KE, Mettenleiter TC, Loewy AD. Single CNS neurons link both central motor and cardiosympathetic systems: a double-virus tracing study. Neuroscience 118: 853-866, 2003.
89. Kuwaki T, Zhang W, Nakamura A, Deng BS. Emotional and statedependent modification of cardiorespiratory function: role of orexinergic neurons. Auton Neurosci Basic Clin 1-2: 11-16, 2008.
90. Laburthe MVT, El Firar A. Orexins/hypocretin and orexin receptors in apoptosis: a mini-review. Acta Physiol (Oxf) 3: 393-402, 2010.
91. Larimer JL. The command hypothesis: a new view using an old example. Trends Neurosci 11: 506-510, 1988.
92. Lee MG, Hassani OK, Jones BE. Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J Neurosci 25: 6716-6720, 2005.
93. Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA. Neuronal glucosensing: what do we know after 50 years? Diabetes 53: 2521-2528, 2004.
94. Liu ZW, Gan G, Suyama S, Gao XB. Intracellular energy status regulates activity in hypocretin/orexin neurones: a link between energy and behavioural states. J Physiol 589: 4157-4166, 2011.
95. Luong LN, Carrive P. Orexin microinjection in the medullary raphe increases heart rate and arterial pressure but does not reduce tail skin blood flow in the awake rat. Neuroscience 202: 209-217, 2012.
96. Malmierca MS. The structure and physiology of the rat auditory system: an overview. Int Rev Neurobiol 56: 147-211, 2003.
97. Manto M, Oulad Ben Taib N. Cerebellar nuclei: key roles for strategically located structures. Cerebellum 9: 17-21, 2010.
98. Martinez RC, Carvalho-Netto EF, Amaral VC, Nunes-de-Souza RL, Canteras NS. Investigation of the hypothalamic defensive system in the mouse. Behav Brain Res 192: 185-190, 2008.
99. Mayer G, Kesper K, Ploch T, Canisius S, Penzel T, Oertel W, Stiasny-Kolster K. Quantification of tonic and phasic muscle activity in REM sleep behavior disorder. J Clin Neurophysiol 25: 48-55, 2008.
100. Mazzocchi G, Malendowicz LK, Gottardo L, Aragona F, Nussdorfer GG. Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade. J Clin Endocrinol Metab 86: 778-782, 2001.
101. Melzer P, Sachdev RN, Jenkinson N, Ebner FF. Stimulus frequency processing in awake rat barrel cortex. J Neurosci 26: 12198-12205, 2006.
102. Mieda M, Sakurai T. Integrative physiology of orexins and orexin receptors. CNS Neurol Disord Drug Targets 8: 281-295, 2009.
103. Mignot E. Sleep, sleep disorders and hypocretin (orexin). Sleep Med 5, Suppl 1: S2-S8, 2004.
104. Mileykovskiy BY, Kiyashchenko LI, Siegel JM. Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46: 787-798, 2005.
105. Mitler MM, Dement WC. Sleep studies on canine narcolepsy: pattern and cycle comparisons between affected and normal dogs (Abstract). Electroencephalogr Clin Neurophysiol 43: 691, 1977.
106. Mobbs CV. The "domino theory" of hunger: the hypothalamus is hot. Cell Metab 5: 1-2, 2007.
107. Mota-Ortiz SR, Sukikara MH, Bittencourt JC, Baldo MV, Elias CF, Felicio LF, Canteras NS. The periaqueductal gray as a critical site to mediate reward seeking during predatory hunting. Behav Brain Res 226: 32-40, 2012.
108. Motta SC, Goto M, Gouveia FV, Baldo MV, Canteras NS, Swanson LW. Dissecting the brain's fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders. Proc Natl Acad Sci USA 106: 4870-4875, 2009.
109. Muschamp JW, Dominguez JM, Sato SM, Shen R, Hull EM. A role for hypocretin (orexin) in male sexual behavior. J Neurosci 11: 2837-2845, 2007.
110. Nakamura A, Zhang W, Yanagisawa M, Fukuda Y, Kuwaki T. Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice. J Appl Physiol 102: 241-248, 2007.
111. Nakamura M. Chronic hypoxic pulmonary hypertension. Nihon Rinsho 59: 1181-1185, 2001.
112. Nakamura T, Uramura K, Nambu T, Yada T, Goto K, Yanagisawa M, Sakurai T. Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic system. Brain Res 873: 181-187, 2000.
113. Nattie JH, Comroe E, Jr. Central chemoreception: then..., now. J Appl Physiol 110: 1-8, 2010.
114. Nattie E, Li A. Central chemoreception in wakefulness and sleep: evidence for a distributed network and a role for orexin. J Appl Physiol 108: 1417-1424, 2010.
115. Nattie E, Li A. Respiration and autonomic regulation and orexin. Prog Brain Res 198: 25-46, 2012.
116. Neilson PD. The problem of redundancy in movement control: the adaptive model theory approach. Psychol Res 55: 99-106, 1993.
117. Newport DJ, Heim C, Owens MJ, Ritchie JC, Ramsey CH, Bonsall R, Miller AH, Nemeroff CB. Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis. Neuropsychopharmacology 28: 569-576, 2003.
118. Nishino S. The hypothalamic peptidergic system, hypocretin/orexin and vigilance control. Neuropeptides 41: 117-133, 2007.
119. Nishino S, Sakurai T. The Orexin/Hypocretin System: Physiology and Pathophysiology. Clifton, NJ: Humana, 2006.
120. Nixon JP, Smale L. A comparative analysis of the distribution of immunoreactive orexin A and B in the brains of nocturnal and diurnal rodents (Abstract). Behav Brain Funct 3: 28, 2007.
121. Nowak KW, Strowski MZ, Switonska MM, Kaczmarek P, Singh V, Fabis M, Mackowiak P, Nowak M, Malendowicz LK. Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes. Int J Mol Med 15: 969-972, 2005.
122. Ohno K, Sakurai T. Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol 29: 70-87, 2008.
123. Oldfield BJ, Allen AM, Davern P, Giles ME, Owens NC. Lateral hypothalamic 'command neurons' with axonal projections to regions involved in both feeding and thermogenesis. Eur J Neurosci 25: 2404-2412, 2007.
124. Oldfield BJ, Giles ME, Watson A, Anderson C, Colvill LM, McKinley MJ. The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat. Neuroscience 110: 515-526, 2002.
125. Olson GC, Krasne FB. The crayfish lateral giants as command neurons for escape behavior. Brain Res 214: 89-100, 1981.
126. Onaka TYK. Role of noradrenergic projections to the bed nucleus of the stria terminalis in neuroendocrine and behavioral responses to fearrelated stimuli in rats. Brian Res 788: 287-293, 1998.
127. Owens MJ, Nemeroff CB. Physiology and pharmacology of corticotropin-releasing factor. Pharmacol Rev 43: 425-473, 1991.
128. Parise EM, Lilly N, Kay K, Dossat AM, Seth R, Overton JM, Williams DL. Evidence for the role of hindbrain orexin-1 receptors in the control of meal size. Am J Physiol Regul Integr Comp Physiol 301: R1692-R1699, 2011.
129. Peever JH, Lai YY, Siegel JM. Excitatory effects of hypocretin-1 (hypocretin-A) in the trigeminal motor nucleus are reversed by NMDA antagonism. J Neurophysiol 89: 2591-2600, 2003.
130. Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 80: 53-83, 2006.
131. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6: 991-997, 2000.
132. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18: 9996-10015, 1998.
133. Pollak GD, Burger RM, Klug A. Dissecting the circuitry of the auditory system. Trends Neurosci 26: 33-39, 2003.
134. Queisser G, Wiegert S, Bading H. Structural dynamics of the cell nucleus: basis for morphology modulation of nuclear calcium signaling and gene transcription. Nucleus 2: 98-104, 2011.
135. Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. J Clin Invest 117: 4022-4033, 2007.
136. Ripley B, Overeem S, Fujiki N, Nevsimalova S, Uchino M, Yesavage J, Di Monte D, Dohi K, Melberg A, Lammers GJ, Nishida Y, Roelandse FW, Hungs M, Mignot E, Nishino S. CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology 57: 2253-2258, 2001.
137. Rodgers RJ, Ishii Y, Halford JC, Blundell JE. Orexins and appetite regulation. Neuropeptides 36: 303-325, 2002.
138. Rouet-Benzineb PRFC, Jarry A, Avondo V, Pouzet C, Yanagisawa M, Laboisse C, Laburthe M, Voisin T. Orexins acting at native OX(1) receptor in colon cancer and neuroblastoma cells or at recombinant OX(1) receptor suppress cell growth by inducing apoptosis. J Biol Chem 44: 45875-45886, 2004.
139. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8: 171-181, 2007.
140. Sakurai T. Roles of orexins and orexin receptors in central regulation of feeding behavior and energy homeostasis. CNS Neurol Disord Drug Targets 5: 313-325, 2006.
141. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92: 573-585, 1998.
142. Sakurai T, Mieda M. Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal. Trends Pharmacol Sci 32: 451-462, 2011.
143. Sakurai T, Mieda M, Tsujino N. The orexin system: roles in sleep/wake regulation. Ann NY Acad Sci 1200: 149-161, 2010.
144. Samson WK, Bagley SL, Ferguson AV, White MM. Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress. Am J Physiol Regul Integr Comp Physiol 292: R382-R387, 2007.
145. Sangal RB, Sangal JM, Belisle C. Longer auditory and visual P300 latencies in patients with narcolepsy. Clin Electroencephalogr 30: 28-32, 1999.
146. Savaskan E, Muller-Spahn F, Meier F, Wirz-Justice A, Meyer P. Orexins and their receptors in the human retina. Pathobiology 71: 211-216, 2004.
147. Scammell TE. Wakefulness: an eye-opening perspective on orexin neurons. Curr Biol 11: R769-R771, 2001.
148. Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol 51: 243-266, 2011.
149. Schreyer S, Buttner-Ennever JA, Tang X, Mustari MJ, Horn AK. Orexin-A inputs onto visuomotor cell groups in the monkey brainstem. Neuroscience 164: 629-640, 2009.
150. Schwimmer H, Stauss HM, Abboud F, Nishino S, Mignot E, Zeitzer JM. Effects of sleep on the cardiovascular and thermoregulatory systems: a possible role for hypocretins. J Appl Physiol 109: 1053-1063, 2010.
151. Sellayah D, Bharaj P, Sikder D. Orexin is required for brown adipose tissue development, differentiation, and function. Cell Metab 14: 478-490, 2011.
152. Shahid IZ, Rahman AA, Pilowsky PM. Orexin and central regulation of cardiorespiratory system. Vitam Horm 89: 159-184, 2012.
153. Siegel JM. The neurotransmitters of sleep. J Clin Psychiatry 65, Suppl 16: 4-7, 2004.
154. Silvani A, Bastianini S, Berteotti C, Lo Martire V, Zoccoli G. Control of cardiovascular variability during undisturbed wake-sleep behavior in hypocretin-deficient mice. Am J Physiol Regul Integr Comp Physiol 302: R958-R964, 2012.
155. Sitskoorn M. The plasticity of the brain: The effect of behavior. Pscholoog 40: 262-267, 2005.
156. Strawn JR, Pyne-Geithman GJ, Ekhator NN, Horn PS, Uhde TW, Shutter LA, Baker DG, Geracioti TD, Jr. Low cerebrospinal fluid and plasma orexin-A (hypocretin-1) concentrations in combat-related posttraumatic stress disorder. Psychoneuroendocrinology 35: 1001-1007, 2010.
157. Swinburne R. Simplicity as Evidence for Truth. Milwaukee, WI: Marquette Univ Press, 1997, p. 71.
158. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Reduced number of hypocretin neurons in human narcolepsy. Neuron 27: 469-474, 2000.
159. Tomasik PJ, Spodaryk M, Sztefko K. Plasma concentrations of orexins in children. Ann Nutr Metab 48: 215-220, 2004.
160. Torterolo P, Ramos OV, Sampogna S, Chase MH. Hypocretinergic neurons are activated in conjunction with goal-oriented survival-related motor behaviors. Physiol Behav 104: 823-830, 2011.
161. Torterolo P, Vanini G, Zhang J, Sampogna S, Chase M. Hypocretinergic fibers and receptors in the inferior colliculus. Sleep Suppl 30: A15, 2007.
162. Torterolo P, Yamuy J, Sampogna S. Hypothalamic neurons that contain hypocretin (orexin) express c-fos during active wakefulness and carbachol-induced active sleep. Sleep Res Online 4: 25-32, 2001.
163. Torterolo P, Yamuy J, Sampogna S, Morales FR, Chase MH. Hypocretinergic neurons are primarily involved in activation of the somatomotor system. Sleep 26: 25-28, 2003.
164. Tsujino N, Sakurai T. Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 61: 162-176, 2009.
165. van den Pol A. Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci 19: 3171-3182, 1999.
166. van den Pol AN, Gao XB, Obrietan K, Kilduff TS, Belousov AB. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. J Neurosci 18: 7962-7971, 1998.
167. Voisin T, El Firar A, Rouyer-Fessard C, Gratio V, Laburthe M. A hallmark of immunoreceptor, the tyrosine-based inhibitory motif ITIM, is present in the G protein-coupled receptor OX1R for orexins and drives apoptosis: a novel mechanism. FASEB J 22: 1993-2002, 2008.
168. Wall J, Xu J, Wang X. Human brain plasticity: an emerging view of the multiple substrates and mechanisms that cause cortical changes and related sensory dysfunctions after injuries of sensory inputs from the body. Brain Res Rev 39: 181-215, 2002.
169. Watson CJ, Soto-Calderon H, Lydic R, Baghdoyan HA. Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness. Sleep 31: 453-464, 2008.
170. Wiersma CA, Ikeda K. Interneurons commanding swimmeret movements in the crayfish, procambarus clarki (girard). Comp Biochem Physiol 12: 509-525, 1964.
171. Williams RH, Burdakov D. Hypothalamic orexins/hypocretins as regulators of breathing. Expert Rev Mol Med 10: e28, 2008.
172. Willie JT, Lim MM, Bennett RE, Azarion AA, Schwetye KE, Brody DL. Controlled cortical impact traumatic brain injury acutely disrupts wakefulness and extracellular orexin dynamics as determined by intracerebral microdialysis in mice. J Neurotrauma In press.
173. Winer JA. Decoding the auditory corticofugal systems. Hear Res 207: 1-9, 2005.
174. Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T, Kilduff TS, Horvath TL, de Lecea L. Interaction between the corticotropin- releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci 24: 11439-11448, 2004.
175. Wong KK, Ng SY, Lee LT, Ng HK, Chow BK. Orexins and their receptors from fish to mammals: a comparative approach. Gen Comp Endocrinol 171: 124-130, 2011.
176. Wu M, Zaborszky L, Hajszan T, van den Pol AN, Alreja M. Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons. J Neurosci 24: 3527-3536, 2004.
177. Xi M, Chase MH. The injection of hypocretin-1 into the nucleus pontis oralis induces either active sleep or wakefulness depending on the behavioral state when it is administered. Sleep 33: 1236-1243, 2010.
178. Xi M, Fung SJ, Lopatto J, Chase MH. Hypocretin-1 (orexin-A) suppresses apnea-induced excitototic processes in the hippocampus. Sleep Suppl 26: A35, 2013.
179. Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38: 701-713, 2003.
180. Yamuy J, Fung SJ, Xi MC, Chase MH. State-dependent control of lumbar motoneurons by the hypocretinergic system. Exp Neurol 221: 335-345, 2010.
181. Yamuy J, Fung SJ, Xi M, Chase MH. Hypocretinergic control of spinal cord motoneurons. J Neurosci 24: 5336-5345, 2004.
182. Yamuy J, Fung SJ, Xi M, Wilson CL, Morales FR, Chase MH. Hypocretin-1-induced effects on spinal cord motoneurons of the cat. Soc Neurosci 903: 257-262, 2001.
183. Yan J, He C, Xia JX, Zhang D, Hu ZA. Orexin-A excites pyramidal neurons in layer 2/3 of the rat prefrontal cortex. Neurosci Lett In press.
184. Yoshida K, McCormack S, Espana RA, Crocker A, Scammell TE. Afferents to the orexin neurons of the rat brain. J Comp Neurol 494: 845-861, 2006.
185. Young JK, Wu M, Manaye KF, Kc P, Allard JS, Mack SO, Haxhiu MA. Orexin stimulates breathing via medullary and spinal pathways. J Appl Physiol 98: 1387-1395, 2005.
186. Yu L, Zhang XY, Zhang J, Zhu JN, Wang JJ. Orexins excite neurons of the rat cerebellar nucleus interpositus via orexin 2 receptors in vitro. Cerebellum 9: 88-95, 2009.
187. Yuan LB, Dong HL, Zhang HP, Zhao RN, Gong G, Chen XM, Zhang LN, Xiong L. Neuroprotective effect of orexin-A is mediated by an increase of hypoxia-inducible factor-1 activity in rat. Anesthesiology 114: 340-354, 2011.
188. Zeitzer JM, Buckmaster CL, Lyons DM, Mignot E. Locomotordependent and -independent components to hypocretin-1 (orexin A) regulation in sleep-wake consolidating monkeys. J Physiol 557: 1045-1053, 2004.
189. Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, de Lecea L, Deisseroth K. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 3: 439-456, 2010.
190. Zhang J, Li B, Yu L, He YC, Li HZ, Zhu JN, Wang JJ. A role for orexin in central vestibular motor control. Neuron 69: 793-804, 2004.
191. Zhang JH, Sampogna S, Morales FR, Chase MH. Age-dependent changes in the midsized neurofilament subunit in sensory-motor systems of the cat brainstem: an immunocytochemical study. J Gerontol A Biol Sci Med Sci 55: B233-B241, 2000.
192. Zhang JH, Sampogna S, Morales FR, Chase MH. Age-related changes of hypocretin in basal forebrain of guinea pig. Peptides 26: 2590-2596, 2005.
193. Zhang JH, Sampogna S, Morales FR, Chase MH. Age-related ultrastructural changes in hypocretinergic terminals in the brainstem and spinal cord of cats. Neurosci Lett 373: 171-174, 2005.
194. Zhang JH, Sampogna S, Morales FR, Chase MH. Orexin (hypocretin)-like immunoreactivity in the cat hypothalamus: a light and electron microscopic study. Sleep 24: 67-76, 2001.
195. Zhang JH, Xi M, Fung SJ, Torterolo P, Sampogna S, Engel JSJ, Chase MH. Tracking hypocretin from the CNS to peripheral organs using nanoparticle technology. Soc Neurosci Abstracts 598-591, 2008.
196. Zhang W, Sakurai T, Fukuda Y, Kuwaki T. Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice. Am J Physiol Regul Integr Comp Physiol 290: R1654-R1663, 2006.
197. Zhu L, Onaka T, Sakurai T, Yada T. Activation of orexin neurones after noxious but not conditioned fear stimuli in rats. Neuroreport 13: 1351-1353, 2002.