Sleep and Wakefulness

Sleep Fundamentals - The Body's Clock

• Sleep: Reversible state of unconsciousness, defined by specific EEG criteria.
• Wakefulness: State of consciousness, actively maintained by Reticular Activating System (RAS).
• Circadian Rhythms (~24h): Endogenous biological rhythms, entrained by zeitgebers.
  • Suprachiasmatic Nucleus (SCN): Hypothalamic master clock. 📌 SCN: "Sun Controller Nucleus".
  • Light: Primary zeitgeber; signals via retinohypothalamic tract to SCN; inhibits melatonin.
  • Melatonin: Pineal gland hormone (from serotonin); secretion ↑ in darkness, ↓ by light.
• Other Zeitgebers: Social cues, meals, physical activity.
• Polysomnography (PSG) Basics: Key diagnostic tool.
  • EEG: Brain waves.
  • EOG: Eye movements.
  • EMG: Muscle tone.

⭐ Melatonin secretion is maximally inhibited by blue-spectrum light and peaks during subjective night.

Sleep Architecture - Journey Through Night

• Sleep Cycle: 4-6 cycles/night, each 90-110 min. NREM predominates early, REM late.
  • 📌 EEG Waves: BATS Drink Blood (Beta [awake], Alpha [drowsy], Theta [N1], Spindles/K-complexes [N2], Delta [N3], Beta [REM]).
• NREM Sleep (Non-Rapid Eye Movement): Stages of progressively deeper sleep.
  • Physiological: ↓HR, ↓BP, ↓RR, ↓Temp.
  • N1 (Light Sleep): Theta waves.
  • N2: Sleep spindles & K-complexes.

    ⭐ Sleep spindles and K-complexes are hallmarks of N2 sleep.

  • N3 (Slow Wave Sleep - SWS): Delta waves >20%. Deepest, restorative sleep.
• REM Sleep (Rapid Eye Movement):
  • EEG: Low voltage, mixed frequency (Beta-like), sawtooth waves.
  • Features: Rapid eye movements, muscle atonia (except diaphragm, extraocular), vivid dreaming, PGO (Pons-Geniculate-Occipital) waves.
• Age-Related Changes: ↓Total sleep, ↓SWS, ↓REM latency, ↑Wake After Sleep Onset (WASO), ↑N1.

Sleep-Wake Neurobiology - Brain's On/Off Switch

Wakefulness Promoting Systems:

• Reticular Activating System (RAS): Core arousal.
• Locus Coeruleus (LC): Norepinephrine (NE).
• Raphe Nuclei (RN): Serotonin (5-HT).
• Tuberomammillary Nucleus (TMN): Histamine.
• Lateral Hypothalamus (LH): Orexin/Hypocretin - stabilizes wake. 📌 Orexin KEEPS you awake.
• Basal Forebrain (BF) & PPT/LDT: Acetylcholine (ACh).

Sleep Promoting Systems:

• Ventrolateral Preoptic Nucleus (VLPO): GABA, Galanin (inhibits wake centers).
• Adenosine: Builds sleep pressure.

REM Sleep:

• REM-ON: Pedunculopontine Tegmental (PPT) & Laterodorsal Tegmental (LDT) nuclei (ACh).
• REM-OFF: LC (NE), RN (5-HT); VLPO (indirectly).

Flip-Flop Model: Mutual inhibition between wake (RAS, LC, etc.) & sleep (VLPO) areas. Orexin stabilizes wakefulness.

⭐ Orexin (hypocretin) deficiency is the primary cause of narcolepsy type 1.

Sleep Disorders Snippets - When Sleep Goes Wrong

• Insomnia: Difficulty initiating/maintaining sleep (sleep-onset, sleep-maintenance types).
• Narcolepsy Type 1: Tetrad: EDS, Cataplexy, Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations. Orexin deficiency; HLA-DQB1*06:02.

  ⭐ Cataplexy in narcolepsy is often triggered by strong emotions.

• Obstructive Sleep Apnea (OSA): Repetitive airway collapse. Snoring, EDS. PSG: AHI >5/hr + symptoms, or >15/hr.
• Parasomnias:

  Feature	NREM (Sleepwalking, Night Terrors)	REM (RBD)
  Age	Children	Elderly
  Stage	SWS (N3)	REM
  Clinical	Amnesia for event	Dream enactment, loss of atonia
  Association	Benign	Synucleinopathies

High‑Yield Points - ⚡ Biggest Takeaways

• REM sleep features muscle atonia, vivid dreams, PGO waves, and an EEG resembling wakefulness.
• NREM Stage N3 (slow-wave sleep) is characterized by delta waves on EEG and is vital for physical restoration.
• The suprachiasmatic nucleus (SCN) in the hypothalamus acts as the primary circadian pacemaker, regulating sleep-wake cycles.
• Orexin/hypocretin from the lateral hypothalamus is crucial for maintaining wakefulness; its deficiency causes narcolepsy.
• Acetylcholine is key for REM sleep initiation and maintenance; serotonin and norepinephrine are important for wakefulness and suppressing REM sleep.
• With ageing, there is typically a decrease in total sleep time, REM sleep percentage, and especially slow-wave sleep (N3).