How does the brain promote wakefulness?

Updated: Sep 11, 2018
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Brain areas critical for wakefulness consist of several discrete neuronal groups centered around the pontine and medullary reticular formation and its extension into the hypothalamus (see the image below). Although diverse in terms of neurochemistry, these cell groups share the features of a diffuse “ascending” projection to the forebrain and a “descending” projection to brainstem areas involved in regulating sleep-wake states. The neurotransmitters involved, along with the main cell groups that produce them, are as follows:

Histamine – histaminergic cells in the tuberomammillary nucleus (TMN) in the posterior hypothalamus

  • Norepinephrine – norepinephrine-producing neurons in the locus coeruleus (LC)

  • Serotonin – serotonergic neurons in the dorsal raphe nuclei (DRN)

  • Dopamine – dopaminergic neurons in the ventral tegmental area (VTA)

  • Acetylcholine – cholinergic neurons of the basal forebrain

    The ascending arousal system. Adapted from Saper e The ascending arousal system. Adapted from Saper et al. Hypothalamic Regulation of Sleep and Circadian Rhythms. Nature 2005;437:1257-1263.

Each region and neurotransmitter contributes to the promotion of wakefulness, but chronic lesions of any one system do not disrupt wakefulness. This suggests a redundant system, wherein the absence of one neurotransmitter may be compensated by the other systems.

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