Skip to main content
SpringerLink
Log in

Orexin Induced Modulation of REM Sleep and Its Loss Associated Patho-Physiological Changes Are Mediated Through Locus Coeruleus

  • Chapter
  • First Online:
Orexin and Sleep

  • 888 Accesses

Abstract

Orexinergic neurons are located in the perifornical (PeF) area and their projections have been reported in many areas in the brain including the hypothalamus and locus coeruleus (LC). Orexin is known to influence many patho-physiological processes, including REM sleep (REMS) and associated processes in health and diseases. Based on the findings/reports from this lab and that of others, we conclude that orexin-induced modulation (loss) of REMS and associated pathophysiological changes are mediated to a large extent at least by influencing the noradrenalin (NA)-ergic neurons in the LC, which possesses REM-OFF neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

EEG:

Electroencephalogram

EMG:

Electromyogram

EOG:

Electrooculogram

LC:

Locus coeruleus

LDT:

Latero-dorsal tegementum

NA:

Noradrenalin

NREMS:

Non-REMS

Orx:

Orexin

OX1R:

Orexin-1 receptor

PeF:

Perifornical area

PPT:

Pedunclo-pontine tegmentum

REMS:

Rapid eye movement sleep

REMSD:

REMS deprivation

TMN:

Tuberomammillary nucleus

References

  • Alam MA, Mallick BN (2008) Glutamic acid stimulation of the perifornical-lateral hypothalamic area promotes arousal and inhibits non-REM/REM sleep. Neurosci Lett 439:281–286

    Article  CAS  PubMed  Google Scholar 

  • Alam MN, Gong H, Alam T, Jaganath R, McGinty D, Szymusiak R (2002) Sleep-waking discharge patterns of neurons recorded in the rat perifornical lateral hypothalamic area. J Physiol 538:619–631

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Allada R, Siegel JM (2008) Unearthing the phylogenetic roots of sleep. Curr Biol 18:R670–R679

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Aristakesian EA (2009) Evolutionary aspects of sleep and stress interaction: phylo-, ontogenetic approach. Zh Evol Biokhim Fiziol 45:598–611

    CAS  PubMed  Google Scholar 

  • Aserinsky E, Kleitman N (1953) Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science 118:273–274

    Article  CAS  PubMed  Google Scholar 

  • Aston-Jones G, Bloom FE (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1:876–886

    CAS  PubMed  Google Scholar 

  • Baldo BA, Daniel RA, Berridge CW, Kelley AE (2003) Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464:220–237

    Article  PubMed  Google Scholar 

  • Bayer L, Eggermann E, Serafin M, Grivel J, Machard D, Muhlethaler M, Jones BE (2005) Opposite effects of noradrenaline and acetylcholine upon hypocretin/orexin versus melanin concentrating hormone neurons in rat hypothalamic slices. Neuroscience 130:807–811

    Article  CAS  PubMed  Google Scholar 

  • Bernard R, Lydic R, Baghdoyan HA (2003) Hypocretin-1 causes G protein activation and increases ACh release in rat pons. Eur J Neurosci 18:1775–1785

    Article  PubMed  Google Scholar 

  • Bernard R, Lydic R, Baghdoyan HA (2006) Hypocretin (orexin) receptor subtypes differentially enhance acetylcholine release and activate g protein subtypes in rat pontine reticular formation. J Pharmacol Exp Ther 317:163–171

    Article  CAS  PubMed  Google Scholar 

  • Berridge CW, Abercrombie ED (1999) Relationship between locus coeruleus discharge rates and rates of norepinephrine release within neocortex as assessed by in vivo microdialysis. Neuroscience 93:1263–1270

    Article  CAS  PubMed  Google Scholar 

  • Beuckmann CT, Sinton CM, Williams SC, Richardson JA, Hammer RE, Sakurai T, Yanagisawa M (2004) Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J Neurosci 24:4469–4477

    Article  CAS  PubMed  Google Scholar 

  • Biswas S, Mishra P, Mallick BN (2006) Increased apoptosis in rat brain after rapid eye movement sleep loss. Neuroscience 142:315–331

    Article  CAS  PubMed  Google Scholar 

  • Bourgin P, Huitron-Resendiz S, Spier AD, Fabre V, Morte B, Criado JR, Sutcliffe JG, Henriksen SJ, de Lecea L (2000) Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci 20:7760–7765

    CAS  PubMed  Google Scholar 

  • Burdakov D, Luckman SM, Verkhratsky A (2005) Glucose-sensing neurons of the hypothalamus. Philos Trans R Soc Lond B Biol Sci 360:2227–2235

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burgess CR, Scammell TE (2012) Narcolepsy: neural mechanisms of sleepiness and cataplexy. J Neurosci 32:12305–12311

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carter ME, de Lecea L (2011) Optogenetic investigation of neural circuits in vivo. Trends Mol Med 17:197–206

    Article  PubMed Central  PubMed  Google Scholar 

  • Carter ME, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S, Deisseroth K, de Lecea L (2010) Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci 13:1526–1533

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carter ME, Brill J, Bonnavion P, Huguenard JR, Huerta R, de Lecea L (2012) Mechanism for Hypocretin-mediated sleep-to-wake transitions. Proc Natl Acad Sci USA 109:E2635–E2644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carter ME, de Lecea L, Adamantidis A (2013) Functional wiring of hypocretin and LC-NE neurons: implications for arousal. Front Behav Neurosci 7:43

    Article  PubMed Central  PubMed  Google Scholar 

  • Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451

    Article  CAS  PubMed  Google Scholar 

  • Chen XW, Mu Y, Huang HP, Guo N, Zhang B, Fan SY, Xiong JX, Wang SR, Xiong W, Huang W, Liu T, Zheng LH, Zhang CX, Li LH, Yu ZP, Hu ZA, Zhou Z (2008) Hypocretin-1 potentiates NMDA receptor-mediated somatodendritic secretion from locus ceruleus neurons. J Neurosci 28:3202–3208

    Article  CAS  PubMed  Google Scholar 

  • Chen L, McKenna JT, Bolortuya Y, Winston S, Thakkar MM, Basheer R, Brown RE, McCarley RW (2010) Knockdown of orexin type 1 receptor in rat locus coeruleus increases REM sleep during the dark period. Eur J Neurosci 32:1528–1536

    Article  PubMed Central  PubMed  Google Scholar 

  • Choudhary RC, Khanday MA, Mitra A, Mallick BN (2014) Perifornical orexinergic neurons modulate REM sleep by influencing locus coeruleus neurons in rats. Neuroscience 279:33–43

    Article  CAS  PubMed  Google Scholar 

  • Chu N, Bloom FE (1973) Norepinephrine-containing neurons: changes in spontaneous discharge patterns during sleeping and waking. Science 179:908–910

    Article  CAS  PubMed  Google Scholar 

  • Clark EL, Baumann CR, Cano G, Scammell TE, Mochizuki T (2009) Feeding-elicited cataplexy in orexin knockout mice. Neuroscience 161:970–977

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Crochet S, Sakai K (1999) Alpha-2 adrenoceptor mediated paradoxical (REM) sleep inhibition in the cat. NeuroReport 10:2199–2204

    Article  CAS  PubMed  Google Scholar 

  • 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 (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322–327

    Article  PubMed Central  PubMed  Google Scholar 

  • Delagrange P, Canu MH, Rougeul A, Buser P, Bouyer JJ (1993) Effects of locus coeruleus lesions on vigilance and attentive behaviour in cat. Behav Brain Res 53:155–165

    Article  CAS  PubMed  Google Scholar 

  • Dement WC (1958) The occurrence of low voltage fast electroencephalogram patterns during behavioral sleep in the cat. Electroencephalogr Clin Neurophysiol 10:291–296

    Article  CAS  PubMed  Google Scholar 

  • Espana RA, Reis KM, Valentino RJ, Berridge CW (2005) Organization of hypocretin/orexin efferents to locus coeruleus and basal forebrain arousal-related structures. J Comp Neurol 481:160–178

    Article  PubMed  Google Scholar 

  • Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, Saper CB, Scammell TE (2001) Fos expression in orexin neurons varies with behavioral state. J Neurosci 21:1656–1662

    CAS  PubMed  Google Scholar 

  • Gagnon JF, Petit D, Latreille V, Montplaisir J (2008) Neurobiology of sleep disturbances in neurodegenerative disorders. Curr Pharm Des 14:3430–3445

    Article  CAS  PubMed  Google Scholar 

  • Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ (2001) Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J Neurosci 21:7273–7283

    CAS  PubMed  Google Scholar 

  • Gerashchenko D, Blanco-Centurion C, Greco MA, Shiromani PJ (2003) Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats. Neuroscience 116:223–235

    Article  CAS  PubMed  Google Scholar 

  • Greco MA, Shiromani PJ (2001) Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats. Brain Res Mol Brain Res 88:176–182

    Article  CAS  PubMed  Google Scholar 

  • Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S, Benham CD, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Shah AS, Hatcher JP, Hatcher PD, Jones DN, Smith MI, Piper DC, Hunter AJ, Porter RA, Upton N (1999) Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci USA 96:10911–10916

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, Sakurai T (2001) Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30:345–354

    Article  CAS  PubMed  Google Scholar 

  • Hobson JA, McCarley RW, Wyzinski PW (1975) Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189:55–58

    Article  CAS  PubMed  Google Scholar 

  • Horvath TL, Peyron C, Diano S, Ivanov A, Aston-Jones G, Kilduff TS, van Den Pol AN (1999) Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J Comp Neurol 415:145–159

    Article  CAS  PubMed  Google Scholar 

  • Ivanov A, Aston-Jones G (2000) Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons. NeuroReport 11:1755–1758

    Article  CAS  PubMed  Google Scholar 

  • Jouvet M (1999) Around the discovery of REM sleep in cats. In: Mallick BN, Inoue S (eds) Rapid eye movement sleep. Marcel Dekker, New York

    Google Scholar 

  • Jouvet-Mounier D, Astic L, Lacote D (1970) Ontogenesis of the states of sleep in rat, cat, and guinea pig during the first postnatal month. Dev Psychobiol 2:216–239

    Article  CAS  PubMed  Google Scholar 

  • Kaur S, Panchal M, Faisal M, Madan V, Nangia P, Mallick BN (2004) Long term blocking of GABA-A receptor in locus coeruleus by bilateral microinfusion of picrotoxin reduced rapid eye movement sleep and increased brain Na-K ATPase activity in freely moving normally behaving rats. Behav Brain Res 151:185–190

    Article  CAS  PubMed  Google Scholar 

  • Kilduff TS, Peyron C (2000) The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Trends Neurosci 23:359–365

    Article  CAS  PubMed  Google Scholar 

  • Kiyashchenko LI, Mileykovskiy BY, Lai YY, Siegel JM (2001) Increased and decreased muscle tone with orexin (hypocretin) microinjections in the locus coeruleus and pontine inhibitory area. J Neurophysiol 85:2008–2016

    CAS  PubMed  Google Scholar 

  • Kostin A, Siegel JM, Alam MN (2014) Lack of hypocretin attenuates behavioral changes produced by glutamatergic activation of the perifornical-lateral hypothalamic area. Sleep 37:1011–1020

    PubMed Central  PubMed  Google Scholar 

  • Kumar R, Bose A, Mallick BN (2012) A mathematical model towards understanding the mechanism of neuronal regulation of wake-NREMS-REMS states. PLoS ONE 7:e42059

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lee MG, Hassani OK, Jones BE (2005) Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J Neurosci 25:6716–6720

    Article  CAS  PubMed  Google Scholar 

  • Li Y, van den Pol AN (2005) Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons. J Neurosci 25:173–183

    Article  CAS  PubMed  Google Scholar 

  • Majumdar S, Mallick BN (2005) Cytomorphometric changes in rat brain neurons after rapid eye movement sleep deprivation. Neuroscience 135:679–690

    Article  CAS  PubMed  Google Scholar 

  • Mallick BN, Inoue S (1999) Rapid eye movement sleep. Marcel Dekker, New York

    Google Scholar 

  • Mallick BN, Singh A (2011) REM sleep loss increases brain excitability: role of noradrenaline and its mechanism of action. Sleep Med Rev 15:165–178

    Article  PubMed  Google Scholar 

  • Mallick BN, Mohan Kumar V, Chhina GS, Singh B (1984) Responses of preoptic neurons to stimulation of caudal and rostral brain stem reticular structures. Brain Res Bull 13:353–356

    Article  CAS  PubMed  Google Scholar 

  • Mallick BN, Kumar VM, Chhina GS, Singh B (1986) Comparison of rostro-caudal brain stem influence on preoptic neurons and cortical EEG. Brain Res Bull 16:121–125

    Article  CAS  PubMed  Google Scholar 

  • Mallick BN, Thankachan S, Islam F (1998) Differential responses of brain stem neurons during spontaneous and stimulation-induced desynchronization of the cortical EEG in freely moving cats. Sleep Res Online 1:132–146

    CAS  PubMed  Google Scholar 

  • Mallick BN, Thankachan S, Islam F (2004) Influence of hypnogenic brain areas on wakefulness- and rapid-eye-movement sleep-related neurons in the brainstem of freely moving cats. J Neurosci Res 75:133–142

    Article  CAS  PubMed  Google Scholar 

  • Mallick BN, Singh A, Khanday MA (2012) Activation of inactivation process initiates rapid eye movement sleep. Prog Neurobiol 97:259–276

    Article  PubMed  Google Scholar 

  • Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK (2001) Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 435:6–25

    Article  CAS  PubMed  Google Scholar 

  • McGinty D, Szymusiak R (1971) Neuroanl unit activity patterns in behaving animals: brain stem and limbic system. Annu Rev Psychol 39:135–168

    Article  Google Scholar 

  • Mehta R, Khanday MA, Mallick BN (2015) REM sleep loss associated changes in orexin-A levels in discrete brain areas in rats. Neurosci Lett 590:62–67

    Article  CAS  PubMed  Google Scholar 

  • Methippara MM, Alam MN, Szymusiak R, McGinty D (2000) Effects of lateral preoptic area application of orexin-A on sleep-wakefulness. NeuroReport 11:3423–3426

    Article  CAS  PubMed  Google Scholar 

  • Mieda M, Yanagisawa M (2002) Sleep, feeding, and neuropeptides: roles of orexins and orexin receptors. Curr Opin Neurobiol 12:339–345

    Article  CAS  PubMed  Google Scholar 

  • Mieda M, Williams SC, Richardson JA, Tanaka K, Yanagisawa M (2006) The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker. Proc Natl Acad Sci USA 103:12150–12155

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mieda M, Hasegawa E, Kisanuki YY, Sinton CM, Yanagisawa M, Sakurai T (2011) Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci 31:6518–6526

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mileykovskiy BY, Kiyashchenko LI, Siegel JM (2005) Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46:787–798

    Article  CAS  PubMed  Google Scholar 

  • Monti JM, D’Angelo L, Jantos H, Barbeito L, Abo V (1988) Effect of DSP-4, a noradrenergic neurotoxin, on sleep and wakefulness and sensitivity to drugs acting on adrenergic receptors in the rat. Sleep 11:370–377

    CAS  PubMed  Google Scholar 

  • Moruzzi G (1972) The sleep-waking cycle, Ergebnisse der Physiologie, Biologischen Chemie und Experimentellen Pharmakologie 64:1–165

    Google Scholar 

  • Muraki Y, Yamanaka A, Tsujino N, Kilduff TS, Goto K, Sakurai T (2004) Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor. J Neurosci 24:7159–7166

    Article  CAS  PubMed  Google Scholar 

  • Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K (1999) Distribution of orexin neurons in the adult rat brain. Brain Res 827:243–260

    Article  CAS  PubMed  Google Scholar 

  • Nauta WJH (1946) Hypothalamic regulation of sleep in rats: an experimental study. J Neurophysiol 9:285–316

    CAS  PubMed  Google Scholar 

  • Nishino S, Sakurai T (eds) (2006) The orexin/hypocretin system: physiology and pathophysiology. Humana Press, New Jersey

    Google Scholar 

  • Nishino S, Okura M, Mignot E (2000) Narcolepsy: genetic predisposition and neuropharmacological mechanisms. REVIEW ARTICLE. Sleep Med Rev 4:57–99

    Article  PubMed  Google Scholar 

  • Nishino S, Sakurai E, Nevsimalova S, Yoshida Y, Watanabe T, Yanai K, Mignot E (2009) Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. Sleep 32:175–180

    PubMed Central  PubMed  Google Scholar 

  • Nunez A, Moreno-Balandran ME, Rodrigo-Angulo ML, Garzon M, De Andres I (2006) Relationship between the perifornical hypothalamic area and oral pontine reticular nucleus in the rat. Possible implication of the hypocretinergic projection in the control of rapid eye movement sleep. Eur J Neurosci 24:2834–2842

    Article  CAS  PubMed  Google Scholar 

  • Ohno K, Sakurai T (2008) Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol 29:70–87

    Article  CAS  PubMed  Google Scholar 

  • Pal D, Mallick BN (2007) Neural mechanism of rapid eye movement sleep generation with reference to REM-OFF neurons in locus coeruleus. Ind J Med Res 125:721–739

    CAS  Google Scholar 

  • Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015

    CAS  PubMed  Google Scholar 

  • 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 (2000) 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

    Article  CAS  PubMed  Google Scholar 

  • Porkka-Heiskanen T, Smith SE, Taira T, Urban JH, Levine JE, Turek FW, Stenberg D (1995) Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep. Am J Physiol 268:R1456–R1463

    CAS  PubMed  Google Scholar 

  • Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF (2006) Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci 26:13400–13410

    Article  CAS  PubMed  Google Scholar 

  • Ranjan A, Biswas S, Mallick BN (2010) Cytomorphometric changes in the dorsal raphe neurons after rapid eye movement sleep deprivation are mediated by noradrenalin in rats. Behav Brain Funct 6:62

    Article  PubMed Central  PubMed  Google Scholar 

  • Roffwarg HP, Muzio JN, Dement WC (1966) Ontogenetic development of the human sleep-dream cycle. Science 152:604–619

    Article  CAS  PubMed  Google Scholar 

  • Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richarson 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 (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior, Cell 92 (1 page following 696)

    Google Scholar 

  • Shouse MN, Staba RJ, Saquib SF, Farber PR (2000) Monoamines and sleep: microdialysis findings in pons and amygdala. Brain Res 860:181–189

    Article  CAS  PubMed  Google Scholar 

  • Siegel JM (1975) REM sleep predicts subsequent food intake. Physiol Behav 15:399–403

    Article  CAS  PubMed  Google Scholar 

  • Siegel JM (2004) The neurotransmitters of sleep. J Clin Psychiatry 65(Suppl 16):4–7

    CAS  PubMed  Google Scholar 

  • Siegel JM, Manger PR, Nienhuis R, Fahringer HM, Pettigrew JD (1998) Monotremes and the evolution of rapid eye movement sleep. Philos Trans R Soc Lond B Biol Sci 353:1147–1157

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Singh S, Mallick BN (1996) Mild electrical stimulation of pontine tegmentum around locus coeruleus reduces rapid eye movement sleep in rats. Neurosci Res 24:227–235

    Article  CAS  PubMed  Google Scholar 

  • Smith MI, Piper DC, Duxon MS, Upton N (2003) Evidence implicating a role for orexin-1 receptor modulation of paradoxical sleep in the rat. Neurosci Lett 341:256–258

    Article  CAS  PubMed  Google Scholar 

  • Stickgold R, Walker MP (2005) Sleep and memory: the ongoing debate. Sleep 28:1225–1227

    PubMed  Google Scholar 

  • Stoyanova II, Rutten WL, le Feber J (2010) Orexin-A and orexin-B during the postnatal development of the rat brain. Cell Mol Neurobiol 30:81–89

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sutcliffe JG, de Lecea L (1999) Novel neurotransmitters for sleep and energy homeostasis. Results Probl Cell Differ 26:239–255

    Article  CAS  PubMed  Google Scholar 

  • Sutcliffe JG, de Lecea L (2000) The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding. J Neurosci Res 62:161–168

    Article  CAS  PubMed  Google Scholar 

  • Sutcliffe JG, de Lecea L (2002) The hypocretins: setting the arousal threshold. Nat Rev Neurosci 3:339–349

    Article  CAS  PubMed  Google Scholar 

  • Thakkar MM, Ramesh V, Cape EG, Winston S, Strecker RE, McCarley RW (1999) REM sleep enhancement and behavioral cataplexy following orexin (hypocretin)-II receptor antisense perfusion in the pontine reticular formation. Sleep Res Online 2:112–120

    CAS  PubMed  Google Scholar 

  • Thankachan S, Islam F, Mallick BN (2001) Role of wake inducing brain stem area on rapid eye movement sleep regulation in freely moving cats. Brain Res Bull 55:43–49

    Article  CAS  PubMed  Google Scholar 

  • Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM (2000) Reduced number of hypocretin neurons in human narcolepsy. Neuron 27:469–474

    Article  CAS  PubMed  Google Scholar 

  • Tsujino N, Sakurai T (2009) Orexin/Hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 61:162–176

    Article  CAS  PubMed  Google Scholar 

  • Vogel GW (1975) A review of REM sleep deprivation. Arch Gen Psychiatry 32:749–761

    Article  CAS  PubMed  Google Scholar 

  • Vogel GW, Feng P, Kinney GG (2000) Ontogeny of REM sleep in rats: possible implications for endogenous depression. Physiol Behav 68:453–461

    Article  CAS  PubMed  Google Scholar 

  • Weinhold SL, Seeck-Hirschner M, Nowak A, Hallschmid M, Goder R, Baier PC (2014) The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Behav Brain Res 262:8–13

    Article  CAS  PubMed  Google Scholar 

  • Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY, Marcus JN, Lee C, Elmquist JK, Kohlmeier KA, Leonard CS, Richardson JA, Hammer RE, Yanagisawa M (2003) Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 38:715–730

    Article  CAS  PubMed  Google Scholar 

  • Wu MF, Gulyani SA, Yau E, Mignot E, Phan B, Siegel JM (1999) Locus coeruleus neurons: cessation of activity during cataplexy. Neuroscience 91:1389–1399

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka A (2006) Afferent system of orexin neuron. In: Nishino S (ed) The Orexin/Hypocretin system: physiology and pathophysiology. Hamana Press, New Jersey, pp 61–69

    Chapter  Google Scholar 

  • Yamanaka A, Muraki Y, Tsujino N, Goto K, Sakurai T (2003) Regulation of orexin neurons by the monoaminergic and cholinergic systems. Biochem Biophys Res Commun 303:120–129

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka A, Muraki Y, Ichiki K, Tsujino N, Kilduff TS, Goto K, Sakurai T (2006) Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner. J Neurophysiol 96:284–298

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Research funding from Indian funding agencies viz. CSIR, DBT, BUILDER support, DST, J.C. Bose fellowship and UGC Resource Networking program are acknowledged.

Author information

Authors and Affiliations

  1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Birendra Nath Mallick, Mudasir Ahmad Khanday & Abhishek Singh

Authors
  1. Birendra Nath Mallick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mudasir Ahmad Khanday
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abhishek Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Birendra Nath Mallick .

Editor information

Editors and Affiliations

  1. Dept. of Molecular Neurosci. & Integrati, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan

    Takeshi Sakurai

  2. Somnogen Canada Inc, President and Chief Executive Officer, Toronto, Ontario, Canada

    S.R. Pandi-Perumal

  3. Dept. Pharmacology & Therapeutics, Clinics Hospital Montevideo School of Medicine, Montevideo, Uruguay

    Jaime M. Monti

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Mallick, B.N., Khanday, M.A., Singh, A. (2015). Orexin Induced Modulation of REM Sleep and Its Loss Associated Patho-Physiological Changes Are Mediated Through Locus Coeruleus. In: Sakurai, T., Pandi-Perumal, S., Monti, J. (eds) Orexin and Sleep. Springer, Cham. https://doi.org/10.1007/978-3-319-23078-8_10

Download citation

Publish with us

Policies and ethics

Search

Navigation