Table 1.

A brief account of the neural circuits and neurotransmitters considered in this work.

Neurotransmitter	Brain region	Notes
His	Tuberomammillary nucleus	Increased during wake periods
		Histamine-deficient mice (HDC ko) show abnormal architecture
		Histamine receptor antagonists increase sleep amounts
		Broad, diffuse projections throughout the brain
		Express mostly Hcrtr2 receptors
NE	Locus coeruleus	Tonic activity (2–3 Hz) during wake periods
		Quiescent during NREM and REM
		Optogenetic activation of LC is sufficient for wakefulness
		Optogenetic inhibition of LC increases amount of sleep
		Strong innervations of neocortex
		Expresses only Hcrtr1 receptors
Hcrt	Lateral hypothalamus	Dysfunction of Hcrt system leads to narcolepsy with cataplexy
		Phasic activity precedes sleep-to-wake transitions
		Quiescent during NREM and REM
		Optogenetic and pharmacogenetic stimulation during sleep increases probability of sleep-to-wake transitions
		Suppresses REM sleep
		Stabilizes wake states by projecting to other neural populations associated with arousal
5-HT	Dorsal raphe	Increased during wake periods
	Raphe magnus	Pharmacologic increase in 5-HT (SSRIs) suppresses REM sleep
		Also affects thermoregulation and respiratory function
		Express Hcrtr1 and Hcrtr2 receptors.
ACh	Basal forebrain	Increased firing during wake and REM periods
	Mesencephalic (LDT and PPTN)	Innervate septum, hippocampus, and cortical neurons
		Express Hcrtr1 and Hcrtr2 receptors
		Fire at low frequencies during NREM
		Increased during the transition to REM sleep and waking
DA	Ventral tegmental area	Increased during wake periods and REM sleep
		Decreased during NREM sleep
		DATko mice show increased sleep amounts
		Express Hcrtr1 and Hcrtr2 receptors
	Substantia nigra	SN projects to striatum. Involved in motor control and habit formation
		Lesions of SN or GP attenuate wakefulness