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Thomas E. Scammell, M.D.

TitleProfessor of Neurology
InstitutionBeth Israel Deaconess Medical Center
DepartmentNeurology
AddressBeth Israel Deaconess Medical Center
Cls 705
330 Brookline Ave
Boston MA 02215
Phone617/667-0833
Fax617/667-0810

 Mentoring 
 current student opportunities
Neurobiology of Sleep[login at prompt]
Available: 07/01/11, Expires: 07/01/15

The Scammell Lab focuses on understanding the neurobiology of sleep. We spend much of our lives asleep, and yet surprisingly little is known about why we sleep and how the brain controls sleep. These are important questions because sleep disorders affect about ¼ of the population, resulting in problematic sleepiness, troublesome behavior during sleep, and miserable sleepless nights. Much of the work in our lab focuses on Narcolepsy, a common cause of chronic sleepiness that is caused by the selective loss of hypothalamic neurons producing the orexin/hypocretin neuropeptides. Possible student projects include: 1) Using anatomic and physiologic techniques to map out the neural circuits through which the orexin peptides control wakefulness and regulate REM sleep. 2) Determining how cholinergic neurons in the pons promote arousal. 3) Examining how pain disrupts sleep and why poor sleep worsens pain. 4) Mapping the circuits through which positive emotions trigger cataplexy (brief episodes of paralysis) in narcoleptic mice. Many projects in the lab use mouse models to understand the function of circuits that control sleep and wakefulness. We use cutting edge physiologic and molecular biologic techniques such as optogenetics, Cre-loxP recombination, construction of new recombinant mice, and tracing of anatomic pathways using conditional expression of fluorescent proteins. We also work with post-mortem human brain tissue to better understand how loss of wake-promoting neurons with traumatic brain injury produces chronic sleepiness in humans.

 completed student projects
Does REM Sleep Influence Cataplexy?
Summer, 05/20/10 - 08/31/10
Circadian Rhythms in Mice with Genetic Ablation of the Orexin Neurons
Summer, 07/01/05 - 09/01/05

 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Poli F, Overeem S, Lammers GJ, Plazzi G, Lecendreux M, Bassetti CL, Dauvilliers Y, Keene D, Khatami R, Li Y, Mayer G, Nohynek H, Pahud B, Paiva T, Partinen M, Scammell TE, Shimabukuro T, Sturkenboom M, van Dinther K, Wiznitzer M, Bonhoeffer J. Narcolepsy as an adverse event following immunization: Case definition and guidelines for data collection, analysis and presentation. Vaccine. 2013 Jan 30; 31(6):994-1007.
    View in: PubMed
  2. Imbach LL, Werth E, Kallweit U, Sarnthein J, Scammell TE, Baumann CR. Inter-hemispheric oscillations in human sleep. PLoS One. 2012; 7(11):e48660.
    View in: PubMed
  3. Burgess CR, Scammell TE. Narcolepsy: neural mechanisms of sleepiness and cataplexy. J Neurosci. 2012 Sep 5; 32(36):12305-11.
    View in: PubMed
  4. Saper CB, Romanovsky AA, Scammell TE. Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci. 2012 Aug; 15(8):1088-95.
    View in: PubMed
  5. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011 Jul; 34(7):845-58.
    View in: PubMed
  6. Dimitrova A, Fronczek R, Van der Ploeg J, Scammell T, Gautam S, Pascual-Leone A, Lammers GJ. Reward-seeking behavior in human narcolepsy. J Clin Sleep Med. 2011 Jun 15; 7(3):293-300.
    View in: PubMed
  7. Scott MM, Marcus JN, Pettersen A, Birnbaum SG, Mochizuki T, Scammell TE, Nestler EJ, Elmquist JK, Lutter M. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res. 2011 Sep 23; 222(2):289-94.
    View in: PubMed
  8. Mochizuki T, Arrigoni E, Marcus JN, Clark EL, Yamamoto M, Honer M, Borroni E, Lowell BB, Elmquist JK, Scammell TE. Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice. Proc Natl Acad Sci U S A. 2011 Mar 15; 108(11):4471-6.
    View in: PubMed
  9. Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2011 Feb 10; 51:243-66.
    View in: PubMed
  10. Scammell TE, Matheson JK, Honda M, Thannickal TC, Siegel JM. Coexistence of narcolepsy and Alzheimer's disease. Neurobiol Aging. 2012 Jul; 33(7):1318-9.
    View in: PubMed
  11. Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010 Dec 22; 68(6):1023-42.
    View in: PubMed
  12. Lim AS, Scammell TE. The trouble with Tribbles: do antibodies against TRIB2 cause narcolepsy? Sleep. 2010 Jul; 33(7):857-8.
    View in: PubMed
  13. Diniz Behn CG, Klerman EB, Mochizuki T, Lin SC, Scammell TE. Abnormal sleep/wake dynamics in orexin knockout mice. Sleep. 2010 Mar; 33(3):297-306.
    View in: PubMed
  14. Baumann CR, Bassetti CL, Valko PO, Haybaeck J, Keller M, Clark E, Stocker R, Tolnay M, Scammell TE. Loss of hypocretin (orexin) neurons with traumatic brain injury. Ann Neurol. 2009 Oct; 66(4):555-9.
    View in: PubMed
  15. Kantor S, Mochizuki T, Janisiewicz AM, Clark E, Nishino S, Scammell TE. Orexin neurons are necessary for the circadian control of REM sleep. Sleep. 2009 Sep; 32(9):1127-34.
    View in: PubMed
  16. Arrigoni E, Mochizuki T, Scammell TE. Activation of the basal forebrain by the orexin/hypocretin neurones. Acta Physiol (Oxf). 2010 Mar; 198(3):223-35.
    View in: PubMed
  17. Clark EL, Baumann CR, Cano G, Scammell TE, Mochizuki T. Feeding-elicited cataplexy in orexin knockout mice. Neuroscience. 2009 Jul 21; 161(4):970-7.
    View in: PubMed
  18. Scammell TE, Mochizuki T. Is low histamine a fundamental cause of sleepiness in narcolepsy and idiopathic hypersomnia? Sleep. 2009 Feb; 32(2):133-4.
    View in: PubMed
  19. Scammell TE, Willie JT, Guilleminault C, Siegel JM. A consensus definition of cataplexy in mouse models of narcolepsy. Sleep. 2009 Jan; 32(1):111-6.
    View in: PubMed
  20. Diniz Behn CG, Kopell N, Brown EN, Mochizuki T, Scammell TE. Delayed orexin signaling consolidates wakefulness and sleep: physiology and modeling. J Neurophysiol. 2008 Jun; 99(6):3090-103.
    View in: PubMed
  21. Baumann CR, Clark EL, Pedersen NP, Hecht JL, Scammell TE. Do enteric neurons make hypocretin? Regul Pept. 2008 Apr 10; 147(1-3):1-3.
    View in: PubMed
  22. España RA, McCormack SL, Mochizuki T, Scammell TE. Running promotes wakefulness and increases cataplexy in orexin knockout mice. Sleep. 2007 Nov; 30(11):1417-25.
    View in: PubMed
  23. Baumann CR, Scammell TE, Bassetti CL. Parkinson's disease, sleepiness and hypocretin/orexin. Brain. 2008 Mar; 131(Pt 3):e91.
    View in: PubMed
  24. Behn CG, Brown EN, Scammell TE, Kopell NJ. Mathematical model of network dynamics governing mouse sleep-wake behavior. J Neurophysiol. 2007 Jun; 97(6):3828-40.
    View in: PubMed
  25. Scammell TE, Saper CB. Orexins: looking forward to sleep, back at addiction. Nat Med. 2007 Feb; 13(2):126-8.
    View in: PubMed
  26. Mochizuki T, Klerman EB, Sakurai T, Scammell TE. Elevated body temperature during sleep in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol. 2006 Sep; 291(3):R533-40.
    View in: PubMed
  27. Scammell TE. The frustrating and mostly fruitless search for an autoimmune cause of narcolepsy. Sleep. 2006 May; 29(5):601-2.
    View in: PubMed
  28. Grady SP, Nishino S, Czeisler CA, Hepner D, Scammell TE. Diurnal variation in CSF orexin-A in healthy male subjects. Sleep. 2006 Mar; 29(3):295-7.
    View in: PubMed
  29. Yoshida K, McCormack S, España RA, Crocker A, Scammell TE. Afferents to the orexin neurons of the rat brain. J Comp Neurol. 2006 Feb 10; 494(5):845-61.
    View in: PubMed
  30. Saper CB, Cano G, Scammell TE. Homeostatic, circadian, and emotional regulation of sleep. J Comp Neurol. 2005 Dec 5; 493(1):92-8.
    View in: PubMed
  31. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005 Oct 27; 437(7063):1257-63.
    View in: PubMed
  32. Scammell TE, Saper CB. Orexin, drugs and motivated behaviors. Nat Neurosci. 2005 Oct; 8(10):1286-8.
    View in: PubMed
  33. Crocker A, España RA, Papadopoulou M, Saper CB, Faraco J, Sakurai T, Honda M, Mignot E, Scammell TE. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Neurology. 2005 Oct 25; 65(8):1184-8.
    View in: PubMed
  34. Anderson MP, Mochizuki T, Xie J, Fischler W, Manger JP, Talley EM, Scammell TE, Tonegawa S. Thalamic Cav3.1 T-type Ca2+ channel plays a crucial role in stabilizing sleep. Proc Natl Acad Sci U S A. 2005 Feb 1; 102(5):1743-8.
    View in: PubMed
  35. Willie JT, Renthal W, Chemelli RM, Miller MS, Scammell TE, Yanagisawa M, Sinton CM. Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. Neuroscience. 2005; 130(4):983-95.
    View in: PubMed
  36. Arrigoni E, Crocker AJ, Saper CB, Greene RW, Scammell TE. Deletion of presynaptic adenosine A1 receptors impairs the recovery of synaptic transmission after hypoxia. Neuroscience. 2005; 132(3):575-80.
    View in: PubMed
  37. Lo CC, Chou T, Penzel T, Scammell TE, Strecker RE, Stanley HE, Ivanov PCh. Common scale-invariant patterns of sleep-wake transitions across mammalian species. Proc Natl Acad Sci U S A. 2004 Dec 14; 101(50):17545-8.
    View in: PubMed
  38. Houghton WC, Scammell TE, Thorpy M. Pharmacotherapy for cataplexy. Sleep Med Rev. 2004 Oct; 8(5):355-66.
    View in: PubMed
  39. Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE. Behavioral state instability in orexin knock-out mice. J Neurosci. 2004 Jul 14; 24(28):6291-300.
    View in: PubMed
  40. Simon DK, Nishino S, Scammell TE. Mistaken diagnosis of psychogenic gait disorder in a man with status cataplecticus ("limp man syndrome"). Mov Disord. 2004 Jul; 19(7):838-40.
    View in: PubMed
  41. España RA, Scammell TE. Sleep neurobiology for the clinician. Sleep. 2004 Jun 15; 27(4):811-20.
    View in: PubMed
  42. Gledhill RF, Bartel PR, Yoshida Y, Nishino S, Scammell TE. Narcolepsy caused by acute disseminated encephalomyelitis. Arch Neurol. 2004 May; 61(5):758-60.
    View in: PubMed
  43. Saper CB, Scammell TE. Modafinil: a drug in search of a mechanism. Sleep. 2004 Feb 1; 27(1):11-2.
    View in: PubMed
  44. Ko EM, Estabrooke IV, McCarthy M, Scammell TE. Wake-related activity of tuberomammillary neurons in rats. Brain Res. 2003 Dec 5; 992(2):220-6.
    View in: PubMed
  45. Chou TC, Scammell TE, Gooley JJ, Gaus SE, Saper CB, Lu J. Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci. 2003 Nov 19; 23(33):10691-702.
    View in: PubMed
  46. Llewellyn-Smith IJ, Martin CL, Marcus JN, Yanagisawa M, Minson JB, Scammell TE. Orexin-immunoreactive inputs to rat sympathetic preganglionic neurons. Neurosci Lett. 2003 Nov 13; 351(2):115-9.
    View in: PubMed
  47. Mochizuki T, Scammell TE. Orexin/Hypocretin: wired for wakefulness. Curr Biol. 2003 Jul 15; 13(14):R563-4.
    View in: PubMed
  48. Scammell TE, Arrigoni E, Thompson MA, Ronan PJ, Saper CB, Greene RW. Focal deletion of the adenosine A1 receptor in adult mice using an adeno-associated viral vector. J Neurosci. 2003 Jul 2; 23(13):5762-70.
    View in: PubMed
  49. Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003 Feb; 53(2):154-66.
    View in: PubMed
  50. Chamberlin NL, Arrigoni E, Chou TC, Scammell TE, Greene RW, Saper CB. Effects of adenosine on gabaergic synaptic inputs to identified ventrolateral preoptic neurons. Neuroscience. 2003; 119(4):913-8.
    View in: PubMed
  51. Kramer A, Yang FC, Snodgrass P, Li X, Scammell TE, Davis FC, Weitz CJ. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signalling. Novartis Found Symp. 2003; 253:250-62; discussion 102-9, 263-6, 281-4.
    View in: PubMed
  52. Overeem S, Scammell TE, Lammers GJ. Hypocretin/orexin and sleep: implications for the pathophysiology and diagnosis of narcolepsy. Curr Opin Neurol. 2002 Dec; 15(6):739-45.
    View in: PubMed
  53. Chou TC, Bjorkum AA, Gaus SE, Lu J, Scammell TE, Saper CB. Afferents to the ventrolateral preoptic nucleus. J Neurosci. 2002 Feb 1; 22(3):977-90.
    View in: PubMed
  54. Kramer A, Yang FC, Snodgrass P, Li X, Scammell TE, Davis FC, Weitz CJ. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science. 2001 Dec 21; 294(5551):2511-5.
    View in: PubMed
  55. Gooley JJ, Lu J, Chou TC, Scammell TE, Saper CB. Melanopsin in cells of origin of the retinohypothalamic tract. Nat Neurosci. 2001 Dec; 4(12):1165.
    View in: PubMed
  56. Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci. 2001 Dec; 24(12):726-31.
    View in: PubMed
  57. Olafsdóttir BR, Rye DB, Scammell TE, Matheson JK, Stefánsson K, Gulcher JR. Polymorphisms in hypocretin/orexin pathway genes and narcolepsy. Neurology. 2001 Nov 27; 57(10):1896-9.
    View in: PubMed
  58. Murray BJ, Matheson JK, Scammell TE. Effects of vagus nerve stimulation on respiration during sleep. Neurology. 2001 Oct 23; 57(8):1523-4.
    View in: PubMed
  59. Scammell TE. Wakefulness: an eye-opening perspective on orexin neurons. Curr Biol. 2001 Oct 2; 11(19):R769-71.
    View in: PubMed
  60. Chou TC, Lee CE, Lu J, Elmquist JK, Hara J, Willie JT, Beuckmann CT, Chemelli RM, Sakurai T, Yanagisawa M, Saper CB, Scammell TE. Orexin (hypocretin) neurons contain dynorphin. J Neurosci. 2001 Oct 1; 21(19):RC168.
    View in: PubMed
  61. Scammell TE, Nishino S, Mignot E, Saper CB. Narcolepsy and low CSF orexin (hypocretin) concentration after a diencephalic stroke. Neurology. 2001 Jun 26; 56(12):1751-3.
    View in: PubMed
  62. 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. 2001 Mar 1; 21(5):1656-62.
    View in: PubMed
  63. Scammell TE, Gerashchenko DY, Mochizuki T, McCarthy MT, Estabrooke IV, Sears CA, Saper CB, Urade Y, Hayaishi O. An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience. 2001; 107(4):653-63.
    View in: PubMed
  64. Oka T, Oka K, Scammell TE, Lee C, Kelly JF, Nantel F, Elmquist JK, Saper CB. Relationship of EP(1-4) prostaglandin receptors with rat hypothalamic cell groups involved in lipopolysaccharide fever responses. J Comp Neurol. 2000 Dec 4; 428(1):20-32.
    View in: PubMed
  65. Scammell TE, Estabrooke IV, McCarthy MT, Chemelli RM, Yanagisawa M, Miller MS, Saper CB. Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci. 2000 Nov 15; 20(22):8620-8.
    View in: PubMed
  66. Murray BJ, Apetauerova D, Scammell TE. Severe acute disseminated encephalomyelitis with normal MRI at presentation. Neurology. 2000 Oct 24; 55(8):1237-8.
    View in: PubMed
  67. Murray BJ, Llinas R, Caplan LR, Scammell T, Pascual-Leone A. Cerebral deep venous thrombosis presenting as acute micrographia and hypophonia. Neurology. 2000 Feb 8; 54(3):751-3.
    View in: PubMed
  68. Lövblad KO, Thomas R, Jakob PM, Scammell T, Bassetti C, Griswold M, Ives J, Matheson J, Edelman RR, Warach S. Silent functional magnetic resonance imaging demonstrates focal activation in rapid eye movement sleep. Neurology. 1999 Dec 10; 53(9):2193-5.
    View in: PubMed
  69. 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. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999 Aug 20; 98(4):437-51.
    View in: PubMed
  70. Scammell T, Gerashchenko D, Urade Y, Onoe H, Saper C, Hayaishi O. Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2. Proc Natl Acad Sci U S A. 1998 Jun 23; 95(13):7754-9.
    View in: PubMed
  71. Scammell TE, Griffin JD, Elmquist JK, Saper CB. Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever. Am J Physiol. 1998 Mar; 274(3 Pt 2):R783-9.
    View in: PubMed
  72. Scammell TE, Matheson J. Modafinil: a novel stimulant for the treatment of narcolepsy. Expert Opin Investig Drugs. 1998 Jan; 7(1):99-112.
    View in: PubMed
  73. Elmquist JK, Scammell TE, Saper CB. Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends Neurosci. 1997 Dec; 20(12):565-70.
    View in: PubMed
  74. Elmquist JK, Breder CD, Sherin JE, Scammell TE, Hickey WF, Dewitt D, Saper CB. Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. J Comp Neurol. 1997 May 5; 381(2):119-29.
    View in: PubMed
  75. Scammell TE, Elmquist JK, Griffin JD, Saper CB. Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways. J Neurosci. 1996 Oct 1; 16(19):6246-54.
    View in: PubMed
  76. Scammell TE, Elmquist JK, Saper CB. Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever. Am J Physiol. 1996 Aug; 271(2 Pt 2):R333-8.
    View in: PubMed
  77. Elmquist JK, Scammell TE, Jacobson CD, Saper CB. Distribution of Fos-like immunoreactivity in the rat brain following intravenous lipopolysaccharide administration. J Comp Neurol. 1996 Jul 15; 371(1):85-103.
    View in: PubMed
  78. Scammell TE, Price KJ, Sagar SM. Hyperthermia induces c-fos expression in the preoptic area. Brain Res. 1993 Aug 6; 618(2):303-7.
    View in: PubMed
  79. Scammell TE, Schwartz WJ, Smith CB. No evidence for a circadian rhythm of protein synthesis in the rat suprachiasmatic nuclei. Brain Res. 1989 Aug 7; 494(1):155-8.
    View in: PubMed
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