Fig. 1

The brain’s overall arousal state is modulated by ascending projections to the cortex and thalamus from nuclei in the brainstem and hypothalamus. These include (i) wake-promoting nuclei that release monoaminergic neurotransmitters (blue), the tuberomammillary nucleus (TMN), the ventral tegmental area (VTA), the dorsal raphe (DR), and the locus coeruleus (LC); (ii) wake-promoting and REM sleep-promoting nuclei that release acetylcholine (green), the laterodorsal tegmentum (LDT) and the pedunculopontine tegmentum (PPT); and (iii) wake-promoting neurons in the lateral hypothalamus (yellow) that release orexin (Orx). These nuclei are all GABAergically inhibited by sleep-promoting neurons (red) in the ventrolateral preoptic area (VLPO) and median preoptic area (MnPO). Excitatory (pointed arrows) and inhibitory (rounded arrows) interactions between nuclei are indicated. Mutual inhibition between sleep-promoting and wake-promoting nuclei forms the basis for the sleep/wake switch