Skip to main content Accessibility help
×
Home
  • Print publication year: 2006
  • Online publication date: November 2009

29 - Animal models for sleep disorders

Summary

Introduction

We spend a significant part (about a third) of our lives sleeping, which is essential to our physical and psychological well-being. Sleep, however, is a fragile state that can easily be impaired by psychological stress or physical illness. For up to 10% of the general population, difficulty falling and/or maintaining sleep occurs several times a week (i.e., chronic insomnia). Some of these problems may be due to existences of obstructive sleep apnea syndrome, a condition that affects over 10% of the population, or due to restless leg syndrome (RLS)/periodic leg movement syndrome (PLMS), sleep-related involuntary leg movements often associated with an abnormal sensation in legs. Excessive daytime sleepiness (EDS), parasomnia, and sleep problems associated with medical/psychiatric conditions are also common. Narcolepsy is a primary EDS disorder affecting about 0.05% of the population. EDS is also often secondary to a severe insomnia associated with obstructive sleep apnea.

Many different pathophysiological/etiological mechanisms for these sleep disorders are considered, and the International Classification of Sleep Disorders (ICSD) lists over 84 different types of disorders (Table 29.1). These sleep-related problems are often chronic and negatively affect the subject's quality of life. In a 24-hr society that encourages sleep deprivation, daytime sleepiness is also an emerging issue even in healthy subjects. Accidents due to sleepiness are now well recognized as a major public hazard. The emergence of clinical sleep medicine has proceeded rapidly during the last 30 years with the awareness of these sleep problems.

Related content

Powered by UNSILO
References
Mellinger, GD, Balter, MB, Uhlenhuth, EH. Insomnia and its treatment: prevelance and correlates. Arch. Gen. Psychiatr. 1985, 42: 225–232.
Young, T. Sleep-disordered breathing in older adults: is it a condition distinct from that in middle-aged adults? Sleep 1996, 19: 529–530.
Allen, RP, Earley, CJ. Restless legs syndrome: a review of clinical and pathophysiologic features. J. Clin. Neurophysiol. 2001, 18: 128–147.
Nishino, S, Mignot, E. Pharmacological aspects of human and canine narcolepsy. Progr. Neurobiol. 1997, 52: 27–78.
American Sleep Disorders Association. International Classification of Sleep Disorders: Diagnostic and Coding Manual. Rochester, MN: American Academy of Sleep Medicine, 2001.
Lin, L, Faraco, J, Li, R, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999, 98: 365–376.
Chemelli, RM, Willie, JT, Sinton, CM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999, 98: 437–451.
Thannickal, TC, Moore, RY, Nienhuis, R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000, 27: 469–474.
Peyron, C, Faraco, J, Rogers, W, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nature Med. 2000, 6: 991–997.
Nishino, S, Ripley, B, Overeem, S, Lammers, GJ, Mignot, E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000, 355: 39–40.
Ford, , Kamerow, DB. Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention? J. Am. Med. Ass. 1989, 262: 1479–1484.
Nishino, S, Dement, WC. Neuropharmacology of sedative-hypnotics and CNS stimulants in sleep medicine. In Psychiatric Clinics of North America: Annual Drug Therapy. Philadelphia, PA: W. B. Saunders, 1998, pp. 85–144.
Black, JE, Brooks, SN, Nishino, S. Narcolepsy and syndromes of primary excessive daytime somnolence. Semin. Neurol. 2004, 24: 271–282.
Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. In Kryger, MH, Roth, T, Dement, WC (eds.) Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: W. B. Saunders, 1994, pp. 667–677.
Guilleminault, C, Anders, TF. The pathophysiology of sleep disorders in pediatrics. II. Sleep disorders in children. Adv. Pediatr. 1976, 22: 151–174.
Mahowald, MW, Schenk, CH. REM Sleep Behavior Disorder, 2nd edn. Philadelphia, PA: W. B. Saunders, 1994.
Roehrs, T, Roth, T. Chronic Insomnia Associated with Circadian Rhythm Disorders, 2nd edn. Philadelphia, PA: W. B. Saunders, 1994.
Carskadon M, Dement WC. Normal human sleep. In Kryger, MH, Roth, T, Dement, WC (eds.) Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: W. B. Saunders, 1994, pp. 16–25.
Borbéry AA. Introduction. In Borbéry, AA, Hayaishi, O, Sejnowski, AJ, Altman, JS (eds.) The Regulation of Sleep. Strasbourg: HFSP, 2000, pp. 17–25.
Borbéry, AA. Sleep Homeostatsis and Models of Sleep Regulation, 2nd edn. Philadelphia, PA: W. B. Saunders, 1994.
Lowrey, PL, Takahashi, JS. Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu. Rev. Genomics Hum. Genet. 2004, 5: 407–441.
King, DP, Takahashi, JS. Molecular genetics of circadian rhythms in mammals. Annu. Rev. Neurosci. 2000, 23: 713–742.
Reppert, SM, Weaver, DR. Molecular analysis of mammalian circadian rhythms. Annu. Rev. Physiol. 2001, 63: 647–676.
Czeisler, CA, Duffy, JF, Shanahan, TL, et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 1999, 284: 2177–2181.
Steriade, M, Contreras, D, Curro Dossi, R, Nunez, A. The slow (<1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks. J. Neurosci. 1993, 13: 3284–3299.
Siegel JM. Brainstem mechanisms generating REM sleep. In Kryger, MH, Roth, T, Dement, WC (eds.) Principles and Practice of Sleep Medicine. Philadelphia, PA: W. B. Saunders, 2000, pp. 112–133.
Jones BE. Basic mechanism of sleep–wake states. In Kryger, MH, Roth, T, Dement, WC (eds.) Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: W. B. Saunders, 1994, pp. 145–162.
Nishino S, Taheri S, Black J, Nofzinger E, Mignot E. The neurobiology of sleep in relation to mental illness. In Charney, DS (ed.) Neurobiology of Mental Illness. New York: Oxford University Press, 2004, pp. 1160–1179.
Sastre, JP, Sakai, K, Jouvet, M. Persistence of paradoxical sleep in the cat after destruction of the pontine gagantocellular tegmental field with kainic acid. C. R. Séances Acad. Sci. D 1979, 289: 959–964. (In French)
Hendricks, JC, Morrison, AR, Mann, GL. Different behaviors during paradoxical sleep without atonia depend on pontine lesion site. Brain Res. 1982, 239: 81–105.
Saper, CB, Chou, TC, Scammell, TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci. 2001, 24: 726–731.
Lugaresi, E, Medori, R, Montagna, P, et al. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. New Engl. J. Med. 1986, 315: 997–1003.
Tobler, I, Deboer, T, Fischer, M. Sleep and sleep regulation in normal and prion protein-deficient mice. J. Neurosci. 1997, 17: 1869–1879.
Toh, KL, Jones, CR, He, Y, et al. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 2001, 291: 1040–1043.
Desautels, A, Turecki, G, Montplaisir, J, et al. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. Am. J. Hum. Genet. 2001, 69: 1266–1270.
Lecendreux, M, Bassetti, C, Dauvilliers, Y, et al. HLA and genetic susceptibility to sleepwalking. Mol. Psychiatr. 2003, 8: 114–117.
Schenck, CH, Garcia-Rill, E, Segall, M, Noreen, H, Mahowald, MW. HLA class II genes associated with REM sleep behavior disorder. Ann. Neurol. 1996, 39: 261–263.
Dauvilliers, Y, Mayer, G, Lecendreux, M, et al. Kleine–Levin syndrome: an autoimmune hypothesis based on clinical and genetic analyses. Neurology 2002, 59: 1739–1745.
Mignot, EJ, Dement, WC. Narcolepsy in animals and man. Equine Vet. J. 1993, 25: 476–477.
Okura, M, Fujiki, N, Ripley, B, et al. Narcoleptic canines display periodic leg movements during sleep. Psychiatr. Clin. Neurosci. 2001, 55: 243–244.
Hendricks, JC, Lager, A, O'Brien, D, Morrison, AR. Movement disorders during sleep in cats and dogs. J. Am. Vet. Med. Assoc. 1989, 194: 686–689.
Hendricks, JC, Kline, LR, Kovalski, RJ, et al. The English bulldog: a natural model of sleep-disordered breathing. J. Appl. Physiol. 1987, 63: 1344–1350.
Panckeri, KA, Schotland, HM, Pack, AI, Hendricks, JC. Modafinil decreases hypersomnolence in the English bulldog, a natural animal model of sleep-disordered breathing. Sleep 1996, 19: 626–631.
Yasuma, F, Kozar, LF, Kimoff, RJ, Bradley, TD, Phillipson, EA. Interaction of chemical and mechanical respiratory stimuli in the arousal response to hypoxia in sleeping dogs. Am. Rev. Respir. Dis. 1991, 143: 1274–1277.
Bakehe, M, Miramand, JL, Chambille, B, Gaultier, C, Escourrou, P. Cardiovascular changes during acute episodic repetitive hypoxic and hypercapnic breathing in rats. Eur. Respir. J. 1995, 8: 1675–1680.
Fletcher, EC, Bao, G. Effect of episodic eucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats. J. Appl. Physiol. 1996, 81: 2088–2094.
Bao, G, Metreveli, N, Fletcher, EC. Acute and chronic blood pressure response to recurrent acoustic arousal in rats. Am. J. Hypertens. 1999, 12: 504–510.
Carley, DW, Trbovic, S, Radulovacki, M. Sleep apnea in normal and REM sleep-deprived normotensive Wistar–Kyoto and spontaneously hypertensive (SHR) rats. Physiol. Behav. 1996, 59: 827–831.
Nakamura, A, Kuwaki, T. Sleep apnea in mice: a useful animal model for study of SIDS? Early Hum. Devel. 2003, 75 (Suppl.): S167–S174.
Carley, DW, Radulovacki, M. Role of peripheral serotonin in the regulation of central sleep apneas in rats. Chest 1999, 115: 1397–1401.
Desarnaud, F, Murillo-Rodriguez, E, Lin, L, et al. The diurnal rhythm of hypocretin in young and old F344 rats. Sleep 2004, 27: 851–856.
Nishino, S, Riehl, J, Hong, J, et al. Is narcolepsy REM sleep disorder? Analysis of sleep abnormalities in narcoleptic Dobermans. Neurosci. Res. 2000, 38: 437–446.
Kaitin, KI, Kilduff, TS, Dement, WC. Evidence for excessive sleepiness in canine narcoleptics. Electroencephalogr. Clin. Neurophysiol. 1986, 64: 447–454.
Sakurai, T, Amemiya, A, Ishil, M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G-protein-coupled receptors that regulate feeding behavior. Cell 1998, 92: 573–585.
Lecea, L, Kilduff, TS, Peyron, C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl Acad. Sci. USA 1998, 95: 322–327.
Mignot, E, Lammers, GJ, Ripley, B, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch. Neurol. 2002, 59: 1553–1562.
Ripley, B, Overeem, S, Fujiki, N, et al. CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology 2001, 57: 2253–2258.
Ripley, B, Fujiki, N, Okura, M, Mignot, E, Nishino, S. Hypocretin levels in sporadic and familial cases of canine narcolepsy. Neurobiol. Dis. 2001, 8: 525–534.
Hara, J, Beuckmann, CT, Nambu, T, et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 2001, 30: 345–354.
Nishino, S, Ripley, B, Overeem, S, et al. Low CSF hypocretin (orexin) and altered energy homeostasis in human narcolepsy. Ann. Neurol. 2001, 50: 381–388.
Fujiki, N, Ripley, B, Yoshida, Y, Mignot, E, Nishino, S. Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin ligand deficient narcoleptic dog. Sleep 2003, 6: 953–959.
Schatzberg, SJ, Barrett, J, Cutter, Kl, Ling, L, Mignot, E. Case study: effect of hypocretin replacement therapy in a 3-year-old Weimaraner with narcolepsy. J. Vet. Internal. Med. 2004, 18: 586–588.
Mieda, M, Willie, JT, Hara, J, et al. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc. Natl Acad. Sci. USA 2004, 101: 4649–4654.
Wittig, R, Zorick, F, Piccione, P, Sicklesteel, J, Roth, T. Narcolepsy and disturbed nocturnal sleep. Clin. Electroencephalogr. 1983, 14: 130–134.
Walters, AS, Picchietti, DL, Ehrenberg, BL, Wagner, ML. Restless legs syndrome in childhood and adolescence. Pediatr. Neurol. 1994, 11: 241–245.
Picchietti, DL, England, SJ, Walters, AS, Willis, K, Verrico, T. Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder. J. Child. Neurol. 1998, 13: 588–594.
Ekbom, K. Restless legs. Acta Scand. (Suppl.) 1945, 158: 1–123.
Nishino, S, Shiba, T, Yoshida, Y, et al. Hypocretin/dopaminergic interactions: pharmacological studies of cataplexy and PLMS in canine narcolepsy. Sleep 2003, 26 (Suppl.): A345–A346.
Reid, MS, Tafti, M, Nishino, S, et al. Local administration of dopaminergic drugs into the ventral tegmental area modulate cataplexy in the narcoleptic canine. Brain Res. 1996, 733: 83–100.
Jouvet, M. Recherche sur les structures nerveuses et les mécanismes responsables des différentes phases du sommeil physiologique. Arch. Ital. Biol. 1962, 100: 125–206.
McGinty, DJ, Sterman, MB. Sleep suppression after basal forebrain lesions in the cat. Science 1968, 160: 1253–1255.
Sakai K, El Mansari M, Lin JG, Zhang JG, Vanni-Mercier G. The posterior hypothalamus in the regulation of wakefulness and paradoxical sleep. In Mancia, M, Marini, G (eds.) The Diencephalon and Sleep. New York: Raven Press, 1990, pp. 171–198.
Economo, C. Encephalitis Lethargica: Its Sequelae and Treatment. London: Oxford Medical Publications, 1931.
Sherin, J, Shiromani, P, McCarley, R, Saper, C. Activation of ventrolateral preoptic neurons during sleep. Science 1996, 271: 216–220.
Lu, J, Greco, MA, Shiromani, P, Saper, CB. Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep. J. Neurosci. 2000, 20: 3830–3842.
Kapas, L, Obal, F Jr, Book, AA, et al. The effects of immunolesions of nerve growth factor-receptive neurons by 192 IgG-saporin on sleep. Brain Res. 1996, 712: 53–59.
Gerashchenko, D, Kohls, MD, Greco, M, et al. Hypocretin-2–saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J. Neurosci. 2001, 21: 7273–7283.
Gerashchenko, D, Chou, TC, Blanco-Centurion, CA, Saper, CB, Shiromani, PJ. Effects of lesions of the histaminergic tuberomammillary nucleus on spontaneous sleep in rats. Sleep 2004, 27: 1275–1281.
Vitaterna, MH, King, DP, Chang, AM, et al. Mutagenesis and mapping of a mouse gene clock, essential for circadian behavior. Science 1994, 264: 719–725.
Naylor, E, Bergmann, BM, Krauski, K, et al. The circadian clock mutation alters sleep homeostasis in the mouse. J. Neurosci. 2000, 20: 8138–8143.
King, DP, Zhao, Y, Sangoram, AM, et al. Positional cloning of the mouse clock gene. Cell 1997, 89: 641–653.
Nolan, PM, Peters, J, Vizor, L, et al. Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource. Mamm. Genome 2000, 11: 500–506.
Berrettini, WH, Ferraro, TN, Alexander, RC, Buchberg, AM, Vogel, WH. Quantitative trait loci mapping of three loci controlling morphine preference using inbred mouse strains. Nature Genet. 1994, 7: 54–58.
Tarricone, BJ, Hingtgen, JN, Belknap, JK, Mitchell, SR, Nurnberger, JI Jr. Quantitative trait loci associated with the behavioral response of B × D recombinant inbred mice to restraint stress: a preliminary communication. Behav. Genet. 1995, 25: 489–495.
Lander, ES, Schork, NJ. Genetic dissection of complex traits. Science 1994, 265: 2037–2048.
Lindblad-Toh, K, Winchester, E, Daly, MJ, et al. Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse. Nature Genet. 2000, 24: 381–386.
Hudson, TJ, Church, DM, Greenaway, S, et al. A radiation hybrid map of mouse genes. Nature Genet. 2001, 29: 201–205.
Franken, P, Chollet, D, Tafti, M. The homeostatic regulation of sleep need is under genetic control. J. Neurosci. 2001, 21: 2610–2621.
Franken, P, Malafosse, A, Tafti, M. Genetic variation in EEG activity during sleep in inbred mice. Am. J. Physiol. 1998, 275: R1127–R1137.
Tafti, M, Chollet, D, Valatx, JL, Franken, P. Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice. J. Sleep Res. 1999, 8(Suppl. 1): 37–43.
Tafti, M, Petit, B, Chollet, D, et al. Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations during sleep. Nature Genet. 2003, 34: 320–325.
Tafti, M, Franken, P, Kitahama, K, et al. Localization of candidate genomic regions influencing paradoxical sleep in mice. NeuroReport 1997, 8: 3755–3758.
Toth, , Williams, RW. A quantitative genetic analysis of slow-wave sleep and rapid-eye movement sleep in CXB recombinant inbred mice. Behav. Genet. 1999, 29: 329–337.
Nadeau, JH, Singer, JB, Matin, A, Lander, ES. Analysing complex genetic traits with chromosome substitution strains. Nature Genet. 2000, 24: 221–225.
Franken, P, Malafosse, A, Tafti, M. Genetic determinants of sleep regulation in inbred mice. Sleep 1999, 22: 155–169.
Cirelli, C, Tononi, G. Gene expression in the brain across the sleep–waking cycle. Brain Res. 2000, 885: 303–321.
Kong, J, Shepel, PN, Holden, CP, et al. Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep. J. Neurosci. 2002, 22: 5581–5587.
Porkka-Heiskanen, T, Kalinchuk, A, Alanko, L, Urrila, A, Stenberg, D. Adenosine, energy metabolism, and sleep. Sci. World J. 2003, 3: 790–798.
Gardi, J, Obal, F Jr, Fang, J, Zhang, J, Krueger, JM. Diurnal variations and sleep deprivation-induced changes in rat hypothalamic GHRH and somatostatin contents. Am. J. Physiol. 1999, 277: R1339–R1344.
Darvasi, A. Experimental strategies for the genetic dissection of complex traits in animal models. Nature Genet. 1998, 18: 19–24.
Su, H, Wang, X, Bradley, A. Nested chromosomal deletions induced with retroviral vectors in mice. Nature Genet. 2000, 24: 92–95.
Capecchi, MR. The new mouse genetics: altering the genome by gene targeting. Trends Genet. 1989, 5: 70–76.
Jaenisch, R. Transgenic animals. Science 1988, 240: 1468–1474.
Williams, RS, Wagner, PD. Transgenic animals in integrative biology: approaches and interpretations of outcome. J. Appl. Physiol. 2000, 88: 1119–1126.
Tobler, I, Gaus, SE, Deboer, T, et al. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 1996, 380: 639–642.
Zhang, J, Obal, F Jr, Fang, J, Collins, BJ, Krueger, JM. Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency in the somatotropic system. Neurosci. Lett. 1996, 220: 97–100.
Wisor, JP, Nishino, S, Sora, I, et al. Dopaminergic role in stimulant-induced wakefulness. J. Neurosci. 2001, 21: 1787–1794.
Parmentier, R, Ohtsu, H, Djebbara-Hannas, Z, et al. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J. Neurosci. 2002, 22: 7695–7711.
Huang, ZL, Qu, WM, Li, WD, et al. Arousal effect of orexin A depends on activation of the histaminergic system. Proc. Natl Acad. Sci. USA 2001, 98: 9965–9970.
Toyota, H, Dugovic, C, Koehl, M, et al. Behavioral characterization of mice lacking histamine H(3)-receptors. M. l. Pharmacol. 2002, 62: 389–397; erratum, M. l. Pharmacol. 2002, 62: 763.
Boutrel, B, Monaca, C, Hen, R, Hamon, M, Adrien, J. Involvement of 5-HT1 A receptors in homeostatic and stress-induced adaptive regulations of paradoxical sleep: studies in 5-HT1 A knock-out mice. J. Neurosci. 2002, 22: 4686–4692.
Laposky, AD, Homanics, GE, Basile, A, Mendelson, WB. Deletion of the GABA(A) receptor beta 3 subunit eliminates the hypnotic actions of oleamide in mice. NeuroReport 2001, 12: 4143–4147.
Boutrel, B, Franc, B, Hen, R, Hamon, M, Adrien, J. Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice. J. Neurosci. 1999, 19: 3204–3212.
Frank, MG, Stryker, MP, Tecott, LH. Sleep and sleep homeostasis in mice lacking the 5-HT2c receptor. Neuropsychopharmacology 2002, 27: 869–873.
Krueger, JM, Takahashi, S, Kapas, L. Cytokines in sleep regulation. Adv. Neuroimmunol. 1995, 5: 171–188.
Fang, J, Wang, Y, Krueger, JM. Effects of interleukin-1 beta on sleep are mediated by the type I receptor. Am. J. Physiol. 1998, 274: R655–R660.
Toth, , Opp, MR. Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2001, 280: R1806–R1814.
Deboer, T, Fontana, A, Tobler, I. Tumor necrosis factor (TNF) ligand and TNF receptor deficiency affects sleep and the sleep EEG. J. Neurophysiol. 2002, 88: 839–846.
Kopp, C, Albrecht, U, Zheng, B, Tobler, I. Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Eur. J. Neurosci. 2002, 16: 1099–1106.
Wisor, JP, O'Hara, BF, Terao, A, et al. A role for cryptochromes in sleep regulation. BMC Neurosci. 2002, 3: 20.
Franken, P, Lopez-Molina, L, Marcacci, L, Schibler, U, Tafti, M. The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity. J. Neurosci. 2000, 20: 617–625.
Kapfhamer, D, Valladares, O, Sun, Y, et al. Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nature Genet. 2002, 32: 290–295.
Willie, JT, Chemelli, RM, Sinton, CM, et al. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 2003, 38: 715–730.
Tobler, I, Kopp, C, Deboer, T, Rudolph, U. Diazepam-induced changes in sleep: role of the alpha 1 GABA(A) receptor subtype. Proc. Natl Acad. Sci. USA 2001, 98: 6464–6469.
Bucan, M, Abel, T. The mouse: genetics meets behaviour. Nature Genet. 2002, 3: 114–123.
Man in ‘t Veld, A, Boomsma, F, Lenders, J, et al. Patients with congenital dopamine beta-hydroxylase deficiency: a lesson in catecholamine physiology. Am. J. Hypertens. 1988, 1: 231–238.
Hunsley, MS, Palmiter, RD. Norepinephrine-deficient mice exhibit normal sleep–wake states but have shorter sleep latency after mild stress and low doses of amphetamine. Sleep 2003, 26: 521–526.
Lewandoski, M. Conditional control of gene expression in the mouse. Nature Genet. 2001, 2: 743–755.
Beuckmann, CT, Sinton, CM, Williams, SC, et al. Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy–cataplexy in the rat. J. Neurosci. 2004, 24: 4469–4477.
Twigger, S, Lu, J, Shimoyama, M, et al. Rat Genome Database (RGD): mapping disease onto the genome. Nucleic Acids Res. 2002, 30: 125–128.
Weiss, B, Davidkova, G, Zhang, SP. Antisense strategies in neurobiology. Neurochem. Int. 1997, 31: 321–348.
Cirelli, C, Pompeiano, M, Arrighi, P, Tononi, G. Sleep–waking changes after c-fos antisense injections in the medial preoptic area. NeuroReport 1995, 6: 801–805.
Xi, MC, Morales, FR, Chase, MH. Evidence that wakefulness and REM sleep are controlled by a GABAergic pontine mechanism. J. Neurophysiol. 1999, 82: 2015–2019.
Thakkar, MM, Ramesh, V, Strecker, RE, McCarley, RW. Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats. Arch. Ital. Biol. 2001, 139: 313–328.
Thakkar, MM, Winston, S, McCarley, RW. A1 receptor and adenosinergic homeostatic regulation of sleep–wakefulness: effects of antisense to the A1 receptor in the cholinergic basal forebrain. J. Neurosci. 2003, 23: 4278–4287.
Fabre, V, Boutrel, B, Hanoun, N, et al. Homeostatic regulation of serotonergic function by the serotonin transporter as revealed by nonviral gene transfer. J. Neurosci. 2000, 20: 5065–5075.
Hendricks, JC, Sehgal, A, Pack, AI. The need for a simple animal model to understand sleep. Progr. Neurobiol. 2000, 61: 339–351.
Borbely, AA, Tobler, I. Sleep regulation: relation to photoperiod, sleep duration, waking activity, and torpor. Progr. Brain Res. 1996, 111: 343–348.
Johnson, CH, Golden, SS, Ishiura, M, Kondo, T. Circadian clocks in prokaryotes. Mol. Microbiol. 1996, 21: 5–11.
Pittendrigh, CS. Circadian systems. I. The driving oscillation and its assay in Drosophila pseudoobscura. Proc. Natl Acad. Sci. USA 1967, 58: 1762–1767.
Moore, RY. Circadian rhythms: basic neurobiology and clinical appplications. Annu. Rev. Med. 1997, 49: 253–266.
Sehgal, A, Price, JL, Man, B, Young, MW. Loss of behavioral rhythms and per RNA oscillations in the Drosophilia mutant timeless. Science 1994, 263: 1603–1605.
Ishiura, M, Kutsuna, S, Aoki, S, et al. Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria. Science 1998, 281: 1519–1523.
Garceau, NY, Liu, Y, Loros, JJ, Dunlap, JC. Alternative initiation of translation and time-specific phosphorylation yield multiple forms of the essential clock protein FREQUENCY. Cell 1997, 89: 469–476.
Shearman, LP, Zylka, MJ, Weaver, DR, Kolakowski, LF Jr, Reppert, SM. Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei. Neuron 1997, 19: 1261–1269.
Sun, ZS, Albrecht, U, Zhuchenko, O, et al. RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell 1997, 90: 1003–1011.
Tei, H, Okamura, H, Shigeyoshi, Y, et al. Circadian oscillation of a mammalian homologue of the Drosophila period gene. Nature 1997, 389: 512–516.
Campbell, SS, Tobler, I. Animal sleep: a review of sleep duration across phylogeny. Neurosci. Biobehav. Rev. 1984, 8: 269–300.
Hendricks, JC. Invited review: Sleeping flies don't lie: the use of Drosophila melanogaster to study sleep and circadian rhythms. J. Appl. Physiol. 2003, 94: 1660–1672; discussion 1673.
Engels, WR. P elements in Drosophila. Curr. Topics Microbiol. Immunol. 1996, 204: 103–123.
Belle, JS, Heisenberg, M. Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. Science 1994, 263: 692–695.
Yin, JC, Vecchio, Del M, Zhou, H, Tully, T. CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 1995, 81: 107–115.
Saudou, F, Hen, R. 5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates. Neurochem. Int. 1994, 25: 503–532.
Nassel, DR. Histamine in the brain of insects: a review. Microsc. Res. Tech. 1999, 44: 121–136.
Nassel, DR. Neuropeptides, amines and amino acids in an elementary insect ganglion: functional and chemical anatomy of the unfused abdominal ganglion. Progr. Neurobiol. 1996, 48: 325–420.
Tobler, I, Neuner-Jehle, M. 24-h variation of vigilance in the cockroach Blaberus giganteus. J. Sleep Res. 1992, 1: 231–239.
Nitz, DA, Swinderen, B, Tononi, G, Greenspan, RJ. Electrophysiological correlates of rest and activity in Drosophila melanogaster. Curr. Biol. 2002, 12: 1934–1940.
Cirelli, C. Searching for sleep mutants of Drosophila melanogaster. BioEssays 2003, 25: 940–949.
Cox, KJ, Fetcho, JR. Labeling blastomeres with a calcium indicator: a non-invasive method of visualizing neuronal activity in zebrafish. J. Neurosci. Methods 1996, 68: 185–191.
Fetcho, JR, O'Malley, DM. Visualization of active neural circuitry in the spinal cord of intact zebrafish. J. Neurophysiol. 1995, 73: 399–406.
Ekstrom, P. Developmental changes in the brainstem serotonergic nuclei of teleost fish and neural plasticity. Cell Mol. Neurobiol. 1994, 14: 381–393.
Ma, PM. Catecholaminergic systems in the zebrafish. I. Number, morphology, and histochemical characteristics of neurons in the locus coeruleus. J. Comp. Neurol. 1994, 344: 242–255.
Ma, PM. Catecholaminergic systems in the zebrafish. II. Projection pathways and pattern of termination of the locus coeruleus. J. Comp. Neurol. 1994, 344: 256–269.
Eriksson, KS, Peitsaro, N, Karlstedt, K, Kaslin, J, Panula, P. Development of the histaminergic neurons and expression of histidine decarboxylase mRNA in the zebrafish brain in the absence of all peripheral histaminergic systems. Eur. J. Neurosci. 1998, 10: 3799–3812.
Liang, MR, Alestrom, P, Collas, P. Glowing zebrafish: integration, transmission, and expression of a single luciferase transgene promoted by noncovalent DNA-nuclear transport peptide complexes. Mol. Reprod. Devel. 2000, 55: 8–13.
Yokogawa, T, Zhang, J, Renier, C, Mignot, E. Characterization of a sleep-like state in adult zebrafish. Sleep 2004, 27(Abstract Suppl.): A84.
Renier, CM, Rosa, FM, Mignot, E. Pharmacogenomics of sleep-promoting drugs in zebrafish. Sleep 2004, 27(Abstract Suppl.): A389.
Faraco, JH, Chan, Y, Mignot, E. Characterization of the hypocretin/orexin ligand and receptor loci in the zebrafish. Sleep 2003, 26(Abstract Suppl.): A422.
Gaus, SE, Faraco, J, Mignot, E. Hypocretin/orexin gene expression in the developing zebrafish. Sleep 2003, 26(Abstract Suppl.): A417–418.
Gaus, SE, Faraco, J, Renier, C, et al. Developing zebrafish through random mutagenesis. Sleep 2004, 27(Abstract Suppl.): A386–387.
Fujiki, N, Morris, L, Mignot, E, Nishino, S. Analysis of onset location, laterality and propagation of cataplexy in canine narcolepsy. Psychiatr. Clin. Neurosci. 2002, 56: 275–276.
Huitron-Resendiz, S, Sanchez-Alavez, M, Gallegos, R, et al. Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice. Brain Res. 2002, 928: 126–137.
Hajdu, I, Obal, F Jr, Fang, J, Krueger, JM, Rollo, CD. Sleep of transgenic mice producing excess rat growth hormone. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002, 282: R70–R76.
Valatx, JL, Douhet, P, Bucchini, D. Human insulin gene insertion in mice: effects on the sleep–wake cycle? J. Sleep Res. 1999, 8(Suppl. 1): 65–68.
Pinzar, E, Kanaoka, Y, Inui, T, et al. Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep. Proc. Natl Acad. Sci. USA 2000, 97: 4903–4907.
Fang, J, Wang, Y, Krueger, JM. Mice lacking the TNF 55 kDa receptor fail to sleep more after TNF-alpha treatment. J. Neurosci. 1997, 17: 5949–5955.
Vyazovskiy, VV, Deboer, T, Rudy, B, et al. Sleep EEG in mice that are deficient in the potassium channel subunit K.v.3.2. Brain Res. 2002, 947: 204–211.
Shiromani, PJ, Basheer, R, Thakkar, J, et al. Sleep and wakefulness in c-fos and fos B gene knockout mice. Brain Res. Mol. Brain Res. 2000, 80: 75–87.
Kapfhamer, D, Valladares, O, Sun, Y, et al. Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nature Genet. 2002, 32: 290–295.