HA is released from histamine-containing neurons of the tuberomammillary nucleus of the posterior thalamus. The cell bodies of hypocretin-producing neurons are localized to the dorsolateral hypothalamus and send projections to all the major brain regions that regulate arousal. The noradrenergic cells of the LC inhibit REM sleep, promote wakefulness, and project to various other arousal-regulating brain regions, including the thalamus, hypothalamus, basal forebrain, and cortex. NE is released from norepinephrine-containing neurons of the locus coeruleus (LC).

5-HT is released from serotonin-containing neurons of the dorsal raphe nucleus. Cortical ACh release is greatest during waking and REM sleep and lowest during NREM sleep.

Neurochemicals such as acetylcholine (ACh), dopamine (DA), norepinephrine (NE), serotonin (5-HT), histamine (HA), and the peptide hypocretin maintain the waking state. Adenosine also promotes sleep by inhibiting wakefulness-promoting neurons localized to the basal forebrain, lateral hypothalamus, and tuberomammillary nucleus. Sleep-promoting neurons in the anterior hypothalamus release GABA, which inhibits wake-promoting regions in the hypothalamus and brainstem. GABA is the primary inhibitory neurotransmitter of the central nervous system (CNS), and it has been well established that activation of GABA-a receptors favors sleep.

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