Why we sleep: the temporal organization of recovery - PubMed (original) (raw)

Figure 1. Activity of Major Neural Networks and Hypothesized Molecular Processes Occurring During Wake, NREM Sleep, and REM Sleep

The different colors denote various neurotransmitter systems: red, norepinephrine (NE), histamine (His), and serotonin (5-HT); orange, acetylcholine (Ach); dark red: hypocretin (Hcrt) peptide; pink, dopamine; dark violet: GABAergic and glutamatergic NREM sleep and REM sleep-on neurons. Anatomical abbreviations: BF, basal forebrain (Ach and GABA populations); LDT, laterodorsal tegmental cholinergic (Ach) nucleus; PPT, mesopontine pedunculopontine tegmental cholinergic (Ach) nucleus; LC, adrenergic (NE) locus coeruleus; RN, serotoninergic (5-HT) raphe nuclei; TMN, histaminergic (His) tuberomammillary nucleus; VTA, dopaminergic ventral tegmental area; mPO, median preoptic hypothalamic (GABA) systems; VLPO, ventrolateral preoptic hypothalamic (GABA) systems; SLC, sublocus coeruleus area (GABA and glutamatergic cell groups); SCN, suprachiasmatic nucleus, Hcrt, hypocretin/orexin containing cell group. Upward and downward arrows represent increased/decreased activity and release for selected neurotransmitter (e.g., Ach, NE, 5-HT, His, and Hcrt) systems or in selected metabolic pathways (e.g., protein biosynthesis) during the corresponding sleep/wake state. (A) Wakefulness. During wakefulness, monoaminergic, hypocretinergic, and cholinergic systems are active and contribute to EEG desynchronization through thalamic and cortical projections. Hypocretin cells excite monoaminergic cells, and possibly cholinergic neurons (the net effect on cholinergic neurons is more difficult to estimate as most hypocretin receptors are mostly located on adjacent GABAergic cells in these regions). Muscle tone (electromyogram or EMG) is variable and high, reflecting movements. Note that dopaminergic cells of the VTA do not significantly change firing rates across sleep and wake, although pattern of firing does, contributing to higher dopaminergic release during wakefulness in the prefrontal cortex. The suprachiasmatic nucleus, the master biological clock, is located close to the optic chiasma, and receives retinal input. Time of the day information is relayed through the ventral subparaventricular zone to the dorsomedial hypothalamus, and other brain areas. Note that the SCN is not labeled in further brain diagrams. We hypothesize that during wake, activity, learning, and many metabolic processes are pushed to maximal, unsustainable levels in almost all neuronal networks to compete behaviorally at optimal times for reproduction and feeding. (B) NREM, slow-wave sleep. GABAergic cells of the basal forebrain (BF), median (mPO) and ventrolateral preoptic (VLPO) hypothalamic area are highly active during NREM sleep. mPO area GABAergic cells may also be involved in thermoregulation. VLPO and other cells inhibit monoaminergic and cholinergic cells during NREM and REM sleep. Upon cessation of sensory inputs and sleep onset, thalamocortical loops from the cortex to the thalamic reticular nucleus and relay neurons contribute to the generation of light NREM sleep. As NREM sleep deepens, slow-wave oscillations appear on the EEG. Muscle tone is low but not abolished in NREM sleep. We hypothesize that during NREM sleep, most of the brain (and most notably the cortex) as well as many peripheral organs are recovering. (C) REM sleep. During REM sleep, hypothalamic and basal forebrain sleep-on cells are active, but glutamatergic cells in the sublocus coeruleus (SLC REM-on neurons) also increase activity. These cells trigger REM atonia through caudal projections, while ventral basal forebrain projections contribute to hippocampal theta. Brainstem cholinergic systems are also active, and stimulate thalamocortical loops to generate EEG desynchronization similar to wakefulness. During REM sleep, EMG is low, indicating paralysis through motoneuron inhibition (tonic REM sleep). Twitches (bursting of EMG and small movements) also occur, with intermittent saccades of rapid eye movements and pontogeniculooccipital electrical waves (phasic REM sleep). We hypothesize that during REM sleep, basic locomotor, sensory, and thermoregulatory circuits are recovering.