Sleep Physiology - MBBS 1st Year

1. Introduction

• Newborn: 16-20 h/day
• Child: 10-12 h/day
• Adolescent: 9-10 h/day
• Young adult: ~7-7.5 h/day
• Elderly (>70 yrs): ~6 h/day

2. How Sleep is Recorded - Polysomnography (PSG)

3. Stages of Sleep (AASM Classification)

NREM Sleep (Non-Rapid Eye Movement)

REM Sleep (Rapid Eye Movement)

• EEG: Low amplitude, mixed frequency (similar to N1 / wakefulness - hence called "paradoxical sleep")
• EOG: Rapid conjugate eye movements in bursts
• EMG: Near-complete muscle atonia (active inhibition of motor neurons - protects us from acting out dreams)
• Dreaming is most vivid and consistently recalled in REM
• Brain metabolic activity approaches waking levels

Adams & Victor's Neurology: "Subjects are easily aroused from REM sleep but arousing a person during stage N3 is more difficult; full arousal may take minutes or more, during which time the subject may be slightly disoriented and confused."

4. Architecture of a Normal Night's Sleep (Hypnogram)

1. Sleep onset → progresses through N1 → N2 → N3 within 45-60 min
2. First REM episode occurs about 90 min after sleep onset
3. NREM and REM then alternate in cycles of 60-160 min (the "ultradian cycle")
4. N3 (slow-wave sleep) predominates in the first third of the night
5. REM episodes get longer toward the end of the night (second half is REM-rich)
6. Setting an alarm clock causes selective REM deprivation (as REM is most prominent late in sleep)

• N1 + N2 = 50-60%
• N3 (slow wave) = 15-25%
• REM = 20-25%
• REM in infancy = up to 50% (important for brain development)

5. Neural Control of Sleep-Wake Cycles

The Flip-Flop Switch Model

• Neurons extend from upper pons → hypothalamus → basal forebrain
• Neurotransmitters used: Norepinephrine, Dopamine, Serotonin, Histamine, Glutamate, Acetylcholine
• Orexin (Hypocretin) neurons in the lateral hypothalamus reinforce and stabilize arousal (loss of orexin neurons → Narcolepsy)
• Some basal forebrain neurons use GABA to inhibit cortical inhibitory interneurons (thereby promoting arousal)

• Ventrolateral Preoptic Nucleus (VLPO) in the hypothalamus - key sleep-promoting site
• Preoptic area and pons neurons use GABA to inhibit the arousal system
• Lateral hypothalamic neurons containing Melanin-Concentrating Hormone (MCH) promote REM sleep

REM Sleep Switch (in brainstem)

• REM-On neurons (upper pons): Use GABA + glutamate; glutamatergic projections cause REM phenomena
  • Projections to medulla/spinal cord → activate inhibitory interneurons (GABA + glycine) → hyperpolarize motor neurons → muscle atonia of REM
  • Projections to forebrain → produce dreams
• REM-Off neurons (lower midbrain): GABAergic; inhibit REM-On neurons
• Cholinergic input favors REM; norepinephrine + serotonin prevent REM
  • (That's why SNRIs and TCAs suppress REM sleep)

6. Homeostatic, Allostatic, and Circadian Regulation

(A) Homeostatic Drive ("Process S")

• The longer you stay awake, the stronger the drive to sleep
• Key mediator: Adenosine - accumulates in the brain during wakefulness
  • Acts on A1 receptors → directly inhibits arousal-promoting neurons
  • Acts on A2a receptors → activates VLPO sleep-promoting neurons
  • Caffeine works by blocking adenosine receptors (A1 and A2a) → blocks sleepiness
• Prostaglandin D2 also accumulates and activates VLPO neurons
• Sleep deprivation → increased N3 (slow-wave) intensity on recovery ("rebound sleep")

(B) Allostatic Drive

• Stress, anxiety, and psychological threats activate the arousal system → insomnia
• Chronic insomnia shows hyperactivation of the ascending arousal system on PET scan

(C) Circadian Rhythm ("Process C")

• Controlled by the Suprachiasmatic Nucleus (SCN) of the anterior hypothalamus
• Intrinsic rhythm of ~25 hours, entrained to 24 hours by light (the most powerful zeitgeber/"time giver")
• SCN → outputs to hypothalamus → impose 24-h rhythms on sleep, temperature, feeding, activity
• Melatonin (from pineal gland) modulates this cyclic activity - rises in darkness, promotes sleep onset
• Destruction of SCN → complete disorganization of sleep-wake cycles

7. Physiological Changes During Sleep

Key clinical point: REM sleep atonia is mediated by GABA and glycine inhibiting motor neurons. REM Sleep Behavior Disorder (RBD) occurs when this paralysis fails - patients physically act out their dreams and may injure themselves or their bed partner.

8. Effects of Age on Sleep

9. Functions of Sleep (Why Do We Sleep?)

• N3 / Slow-wave sleep: Physical restoration, growth hormone secretion, immune function
• REM sleep: Memory consolidation, emotional processing, brain maturation (especially in infancy)
• Overall sleep: Metabolic regulation (glucose, insulin), immune response, cardiovascular health, cognitive function

Consequences of Sleep Deprivation

• Impaired cognition, reaction time, vigilance
• Glucose intolerance → risk of diabetes, metabolic syndrome
• Obesity, immune suppression, atherosclerosis
• Increased risk of cardiovascular disease, Alzheimer's disease, stroke

10. Quick Memory Tricks for Exams

• "BASK in sleep": Brain waves slow down in NREM (B-N1, A-N2 spindles, S-N3 slow wave, K-K complex)
• "REM = Rapid + Relaxed muscles + Real dreams"
• Adenosine = sleep pressure; Caffeine = adenosine blocker = wakefulness
• VLPO = sleep ON; SCN = body clock; Orexin = wake stabilizer
• First 1/3 of night = N3 dominant; Last 1/3 = REM dominant
• Sleep spindles + K complexes = N2 (the most common stage of sleep)