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Neurobiology of Normal Sleep and Wakefulness

Review the neuronal systems that play important roles in sleep and wakefulness, including the role of histamine in sleep-wake state stability.

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.1-5 Review how the brain regulates these states to ensure that elements of one state do not intrude into another.

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The Role of Histamine in Sleep and Wakefulness

In the brain, histamine neurons originate only in the hypothalamus and are thought to play an important role in sleep-wake state stability.3,6 Learn how histamine has been shown to help promote and stabilize wakefulness.3,6,7

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Sleep-Wake State Stability

Brush up on the characteristics of normal sleep and wakefulness.

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Role of the Hypothalamus

Learn about neuronal systems that help regulate sleep and wakefulness.

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Histamine

There’s more to know about the role of histamine in regulating wakefulness.

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  1. Schwartz MD, Kilduff TS. The neurobiology of sleep and wakefulness. Psychiatr Clin North Am. 2015;38(4):615-644.
  2. Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
  3. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
  4. Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378.
  5. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
  6. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
  7. 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

Performance of routine tasks without awareness.

Sudden and brief loss of muscle tone, often triggered by strong emotions or certain situations. Narcolepsy with cataplexy is known as narcolepsy type 1.

Complete collapse to the ground; nearly all skeletal muscles are involved.

Only certain muscle groups are involved.

Biological clock mechanism that regulates the 24-hour cycle in the physiological processes of living beings. It is controlled in part by the SCN in the hypothalamus and is affected by the daily light-dark cycle.

Frequent awakenings and inappropriate transitions between states of sleep and wakefulness during nighttime sleep.

The inability to stay awake and alert during the day.

A neurotransmitter in the brain that supports wakefulness.

Vivid, realistic, and sometimes frightening dream-like events that occur when falling asleep.

Also known as orexin. A neuropeptide that supports wakefulness and helps suppress non-REM sleep and REM sleep.

Primary brain region for regulating the timing of sleep-wake states.

Unintentionally falling asleep due to excessive daytime sleepiness. Also known as “sleep attacks.”

Brief, unintentional lapses into sleep or loss of awareness.

A validated objective measure of the tendency to fall asleep in quiet situations.

People living with narcolepsy type 1 have low levels of hypocretin.

Narcolepsy without cataplexy; the cause of narcolepsy type 2 is unknown.

A state of sleep characterized by slower-frequency, more synchronized neuronal activity and decreased muscle tone. Deep stages help to restore the body.

A multiparameter test that monitors physiologic signals during sleep; used as a diagnostic tool in sleep medicine.

A state of sleep characterized by fast-frequency, desynchronized activity on EEG, vivid dreams, and loss of muscle tone. Normally occurs 60-90 minutes after sleep onset. Also known as “paradoxical sleep.”

Brief loss of control of voluntary muscles with retained awareness at sleep-wake transitions.

An abnormal sleep phenomenon characterized by REM sleep occurrence within 15 minutes of sleep onset; may occur during nighttime sleep or daytime napping.

A group of neurons located in the hypothalamus that are essential for promoting non-REM sleep. These neurons project to all wake-promoting regions to inhibit wakefulness and promote non-REM sleep during the night.

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US-NAR-2300169/Nov 2023

US-NAR-2300169/Nov 2023