Know Narcolepsy Video Library
Learn more about the neurobiology of sleep, wakefulness, and narcolepsy and hear real people living with narcolepsy describe the impact of the disorder.
Neurobiology of Sleep and Wakefulness and Pathophysiology of Narcolepsy
Sleep-Wake State Instability Throughout the Day
People living with narcolepsy can experience multiple intrusions of non-REM sleep and REM sleep throughout the day.1-4 Gain more insight on the impact of ongoing sleep-wake state instability in narcolepsy.
The Importance of Histamine in Stabilizing Wakefulness
Histamine neurons may play an important role in sustaining wakefulness for long periods during the day. Review study results that suggest increased activation of histamine neurons may help stabilize wakefulness in narcolepsy.5,6
The Pathophysiology of Cataplexy
Cataplexy occurs when the muscle atonia associated with REM sleep intrudes into wakefulness during the day.7,8 Learn about the neuronal processes that allow strong emotions to trigger a loss of muscle tone in people living with narcolepsy.7,9
Exploring Histamine in Sleep-Wake State Stability
Dr. Thomas Scammell
Thomas Scammell, MD, from Beth Israel Deaconess Medical Center, Boston Children's Hospital, and Harvard Medical School, discusses key data from several animal studies that support why histamine plays an important role in disorders characterized by sleep-wake state instability, such as narcolepsy.10,11
The Pathophysiology of Narcolepsy
Narcolepsy is most often caused by the loss of hypocretin.11,12 This loss can cause the boundaries between wakefulness, non-REM sleep, and REM sleep to become unstable, allowing elements of one state to intrude into another and the transitions between states to become frequent and unpredictable.1,7,11,13,14
The Neurobiology of Normal Sleep and Wakefulness
A normal sleep-wake cycle requires the coordinated activity of several neuronal systems that regulate the timing and stability of three distinct states: wakefulness, non-REM sleep, and REM sleep.6,11,13,15,16 Learn about how the brain regulates these states to ensure that elements of one state do not intrude into another.
The Role of Histamine in Sleep and Wakefulness
In the CNS, histamine neurons originate only in the hypothalamus and are thought to play an important role in sleep-wake state stability.6,10 Learn how histamine has been shown to help promote and stabilize wakefulness.,6,10,17
Excessive Daytime Sleepiness (EDS)
Excessive Daytime Sleepiness and Its Daily Impact
Excessive daytime sleepiness has significantly affected Nicki’s life, especially due to “surprise naps” that have caused her to sleep through her own birthday celebration.
Recognizing Narcolepsy and Excessive Daytime Sleepiness
In college, Matt recognized that he was always the first one to leave the party, but he didn’t know it was because of excessive daytime sleepiness associated with narcolepsy.
People With Narcolepsy Are Often Misunderstood
Emily, Scott, Sharon, & Sean
Four Personal Stories: Four people living with narcolepsy share their experience of what excessive daytime sleepiness (EDS) feels like for them.
What Cataplexy Can Feel Like
Nicki describes what triggers her cataplexy and what it feels like when she loses muscle control.
Emotions That Can Trigger Cataplexy Attacks
Cataplexy attacks have interfered withbig moments in Sean’s personal and professional life, like when he got engaged. Narcolepsy with cataplexy affects everyone differently, but attacks are often brought on by strong emotions.
Avoiding Emotions to Control Cataplexy
Partial cataplexy in his face has impacted Sean’s life. Avoiding emotions to control attacks has become part of his personality.
Social Situations Triggered My Cataplexy
After experiencing cataplexy while holding her infant son, Sharon started to avoid social situations.
Biggest Impact of Narcolepsy
Scott shares why he believes narcolepsy changed the way his friends and family saw him and how the disorder set the course for his life today.
A Parent’s Perspective: Being a Parent With Narcolepsy
Scott, a stay-at-home dad, shares his journey navigating fatherhood while living with narcolepsy.
- Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68(6):1023-1042.
- Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE. Behavioral state instability in orexin knock-out mice. J Neurosci. 2004;24(28):6291-6300.
- Pillen S, Pizza F, Dhondt K, Scammell TE, Overeem S. Cataplexy and its mimics: clinical recognition and management. Curr Treat Options Neurol. 2017;19(6):23.
- Bassetti C, Aldrich MS. Narcolepsy, idiopathic hypersomnia, and periodic hypersomnias. In: Culebras A, ed. Sleep Disorders and Neurological Disease. New York, NY: Marcel Dekker; 2000:323-354.
- Mochizuki T, Arrigonia E, Marcus JN, et al. Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice. Proc Natl Acad Sci. 2011;108(11):4471-4476.
- Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
- Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
- Dauvilliers Y, Siegel JM, Lopez R, Torontali ZA, Peever JH. Cataplexy—clinical aspects, pathophysiology and management strategy. Nat Rev Neurol. 2014;10(7).
- Szabo S, Thorpy MJ, Mayer G, Peever JH, Kilduff TS. Neurobiological and immunogenetic aspects of narcolepsy: implications for pharmacotherapy. Sleep Med Rev. 2019;43:23-36.
- Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
- España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
- Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep. 2002;25(2):197-202.
- Schwartz JRL, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6:367-378.
- Broughton R, Valley V, Aguirre M, Roberts J, Suwalski W, Dunham W. Excessive daytime sleepiness and the pathophysiology of narcolepsy-cataplexy: a laboratory perspective. Sleep. 1986;9:205-215.
- Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
- Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
- Scammell TE, Jackson AC, Franks NP, Wisden W, Dauvilliers Y. Histamine: neural circuits and new medications. Sleep. 2019;42(1). doi: 10.1093/sleep/zsy183.