“Never in a million years could I have envisioned my life going so far off the intended course.” – Scott
Advancements in the understanding of narcolepsy are happening. Sign Up Now »
The Neurobiology of Sleep, Wakefulness, and Narcolepsy
The Normal Neurobiology of Sleep and Wakefulness
Optimal health and cognitive function require the coordinated activity of several neuronal systems that regulate the timing and stability of three distinct states: wakefulness, non-REM sleep, and REM sleep.1-5 Wakefulness usually occurs during the day, while non-REM sleep and REM sleep generally occur at night.2,3 Learn about these states and how the brain regulates them to ensure that elements of one state do not intrude into another.
There’s more to know about how the brain regulates sleep and wakefulness

The Pathophysiology of Narcolepsy
Narcolepsy is most often caused by the loss of hypocretin.6,7 This loss can lead to insufficient activation of wake-promoting neurons and insufficient inhibition of non-REM sleep-promoting neurons and REM sleep-promoting neurons, leading to sleep-wake state instability.3,6,8,9 The boundaries between wakefulness, non-REM sleep, and REM sleep become unstable, allowing elements of one state to intrude into another, and the transitions between states to become frequent and unpredictable.4,6,8-10
There’s more to know about how narcolepsy affects sleep and wakefulness

The Role of Histamine in Sleep and Wakefulness
In the central nervous system, histamine neurons originate only in the hypothalamus and are thought to play an important role in the regulation of sleep-wake state stability.3,11 Learn how histamine has been shown to help promote and stabilize wakefulness.3,11,12
There’s more to know about the role of histamine in regulating wakefulness

- Schwartz MD, Kilduff TS. The neurobiology of sleep and wakefulness. Psychiatr Clin North Am. 2015;38(4):615-644
- Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
- Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
- Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378.
- Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
- 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.
- Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437(7063):1257-1263.
- Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
- 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.
- Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
- 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.