What is the physiology of sleep in a typical adult?

Physiology of Sleep in Adults

Sleep Architecture and Stages

Sleep is an active neurological state composed of two distinct phases—non-rapid eye movement (NREM) and rapid eye movement (REM) sleep—that alternate in approximately 90-minute cycles throughout the night. 1, 2, 3

NREM Sleep Structure

• NREM sleep is subdivided into three stages (N1, N2, N3), representing progressively deeper levels of sleep 3, 4
• Stage N1 represents the lightest sleep, serving as the transition from wakefulness 4
• Stage N2 is characterized by specific electroencephalogram features including K-complexes and sleep spindles 5
• Stage N3 (also called slow-wave or "deep sleep") features delta waves and predominates in the first half of the night 1, 4
• The ventrolateral preoptic nucleus of the hypothalamus and other basal forebrain areas generate NREM sleep 3, 6

REM Sleep Characteristics

• REM sleep is characterized by rapid eye movements, muscle atonia (paralysis), and desynchronized EEG activity resembling wakefulness 3, 4
• REM sleep concentrates in the last half of the night, with longer and more intense periods occurring toward morning 1, 2
• The pedunculopontine and lateral dorsal tegmental areas, interacting with the dorsal raphe nucleus and locus coeruleus, generate REM sleep 6
• During REM sleep, vivid dreaming typically occurs, with normal muscle atonia preventing dream enactment 1

Sleep-Wake Regulation

Homeostatic Process

• Sleep need accumulates during wakefulness through a homeostatic process, creating increasing sleep pressure the longer one stays awake 7, 8
• This homeostatic drive enhances sleep depth and consolidation, particularly increasing slow-wave sleep after prolonged wakefulness 7

Circadian Process

• The suprachiasmatic nucleus (SCN) of the hypothalamus serves as the master circadian pacemaker, coordinating sleep-wake timing over approximately 24 hours 3, 7, 6
• The pineal gland, regulated by the SCN, secretes melatonin in response to darkness, promoting sleep initiation 6
• Light exposure is the primary external synchronizer (zeitgeber) that entrains the circadian system to the environmental day-night cycle 7
• Photosensitive retinal ganglion cells detect light and transmit signals to the SCN to maintain circadian alignment 9

Neurotransmitter Systems

Wake-Promoting Neurotransmitters

• Histamine, hypocretin (orexin), norepinephrine, serotonin, dopamine, acetylcholine, and glutamate promote wakefulness and arousal 3
• These neurotransmitters are released by specific brainstem and hypothalamic nuclei that maintain cortical activation 3

Sleep-Promoting Neurotransmitters

• Gamma-aminobutyric acid (GABA) is the primary sleep-promoting neurotransmitter, inhibiting wake-promoting systems 3
• Adenosine accumulates during wakefulness and promotes sleep by inhibiting wake-active neurons 8

Physiological Changes During Sleep

• Significant autonomic and somatic nervous system changes occur across all body systems during sleep 4
• Metabolic rate decreases, supporting energy conservation as a key sleep function 8
• Immune system modulation occurs during sleep, with sleep deprivation impairing immune responses 7, 8
• Brain waste clearance increases during sleep through the glymphatic system, removing metabolic byproducts accumulated during wakefulness 8
• Synaptic plasticity is modulated during sleep, consolidating memory and learning 7, 8

Sleep Cycle Organization

• A complete sleep cycle lasts approximately 90 minutes, with 4-5 cycles occurring during a typical night 2, 6
• The proportion of NREM versus REM sleep shifts across the night: early cycles contain more deep NREM sleep (N3), while later cycles contain progressively more REM sleep 1
• This cyclic organization is driven by reciprocal interactions between REM-promoting and REM-inhibiting neuronal populations 3

Age-Related Considerations

• Sleep architecture remains relatively stable in healthy adults, though most significant changes occur between ages 19-60 2, 9
• After age 60, healthy individuals experience more modest changes, including decreased total sleep time, reduced sleep efficiency, and decreased slow-wave and REM sleep 2, 9
• Circadian rhythm amplitude weakens with aging due to neuronal loss in the SCN, resulting in earlier sleep timing (phase advance) and reduced tolerance to schedule shifts 9

Clinical Pitfalls

• Sleep interruptions by prolonged wakefulness can fragment the normal 90-minute REM-NREM cycles, disrupting sleep architecture 2
• Medical and psychiatric comorbidities exacerbate sleep disruption beyond normal aging effects, but represent independent problems requiring specific treatment 9
• Certain medications (tricyclic antidepressants, MAO inhibitors, SSRIs) suppress REM sleep, altering normal sleep architecture 2
• Sedative-induced sleep may not provide the same restorative benefits as natural sleep, though this remains uncertain 5