Fig. 2

Summary of the sleep–wake circuitry and impact on NREM, REM and wake states. Briefly, neuromodulation from cholinergic (REM-active, wake-active), noradrenergic (wake and arousal) and serotonergic (in general wake-promoting, neuromodulatory sleep-promoting functions) neurons signals to the hypothalamus and ascending pathways to regulate the sleep–wake balance. Hypothalamic orexinergic and histaminergic neurons promote wake, and MCH promotes sleep. GABAergic (VLPO, POA, PZ) and glutamatergic (PB, BF, PPT/LDT) neurons facilitate sleep- and wake-states, respectively; though GABA can be wake-promoting in certain instances. See Sect. "Sleep-regulating centers and neurodegeneration" for further details [165,166,167,168,169,170,171,172]. Regions are not to scale nor laid out anatomically. Arrows indicate activation signal to the efferent region and flat ends indicate inhibitory signal. Synaptic connections are colored by behavioral state: black dashed lines (ascending neuromodulatory activity with broad effects), red (wake and/or arousal), light red (wake- and REM-active), and blue (NREM and/or SWS). Abbreviations: acetylcholine (ACh); basal forebrain (BF); dorsal raphe nucleus (DRN); glutamate (glut); histamine (hist); lateral hypothalamus (LH); median preoptic nucleus (MnPO); melanin-concentrating hormone (MCH); noradrenaline (NA); non-rapid eye movement sleep (NREM); parabrachial nucleus (PB); parafacial zone (PZ); parvalbumin (PVB); pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT); preoptic area (POA); polysomnography (PSG); rapid eye movement (REM); serotonin (5-HT); slow wave sleep (SWS) somatostatin (SST); suprachiasmatic nucleus (SCN); tuberomammillary nucleus (TMN); vasoactive intestinal polypeptide (VIP); vasopressin (VP); ventrolateral preoptic area (VLPO). Created with BioRender.com