L27: Chronobiology

Question 1

On average, every 90 minutes, sleep moves from stages to stages. What are the stages in the normal sleep cycle?

Answer 1

• Stage 1
• Stage 2
• Stage 3 –> deep sleep, wake up refreshed
• Stage 4 –> deep sleep, wake up refreshed
• REM –> dream stage

*as night progresses, REM increases, and stages 3 & 4 decrease.

Question 2

Electroencephalogram (EEG) can measure sleep patterns. List what you expect to see on EEG in wakefulness, Non-REM sleep, and REM sleep.

Answer 2

Wakefulness

• alert –> low V, fast random activity = β waves
• awake but drowsy –> low V, fast random activity = α waves

Non-REM sleep

• Stage 1 –> lightest sleep, high F, low V = θ waves
• Stage 2 –> light sleep = sleep spindles & K complexes
• Stage 3 –> deep/slow wave sleep (SWS) = Δ waves (20-50%)
• Stage 4 –> deepest sleep = Δ waves (>50%)

REM sleep –> random, fast waves w/ sawtooth waves; EEG appears awake, paralysis occurs, dreams occur, eyes move, erections occur, sympathetic tone dominates

Question 3

What are some theories involving dreams?

Answer 3

• unconscious thoughts, drives, wishes
• consolidation of memory from the day
• removing unwanted memories from the day

Question 4

Explain what aging does to sleep.

Answer 4

Older people spend less time in stages 3 & 4 (deep restful sleep), and more time in stages 1 & 2. Therefore, older people nap. But average sleep time remains 7-8 hrs.

Question 5

What secretes melatonin? What happens when melatonin binds to the 2 different melatonin receptors (MT-1 receptors vs MT-2 receptors)?

Answer 5

• loss of light will cause pineal gland to produce melatonin, Melatonin is a somnogen (will induce sleepiness)
• melatonin + MT-1 receptors –> will decrease sympathetic tone, decrease brain activity
• melatonin + MT-2 receptors –> will regulate 24 hr circadian clock

Question 6

When does cortisol levels increase and what does it signal?

Answer 6

Cortisol levels increase at 4 or 5 am, and increased cortisol levels will signal the brain to wake up.

Question 7

What are the 6 NTs that play a role in normal wakefulness?

Answer 7

• acetylcholine
• glutamate
• NE
• dopamine
• histamine
• serotonin

Question 8

What is the effect of stroke on neurotransmitters that keep us awake?

Answer 8

Stroke will cause decreased release of NTs regulating wakefulness, inducing sleepiness.

Question 9

What secretes acetylcholine? When do we have increased acetylcholine?

Answer 9

Basal forebrain & Laterodorsal tegmental nuclei (LDT) and pedunculopontine tegmental nuclei (PPT) secrete acetylcholine. Acetylcholine is secreted during wakefulness & REM.

Question 10

When we are awake, LC secretes NE to maintain wakefulness. What is NE’s effect on atttention & task performance? What does this say about people with ADHD?

Answer 10

NE will optimize attention and task performance while awake. People with ADHD can’t maintain attention; it could be b/c they are not secreting NE as much.

Question 11

People who have insomnia & anxiety at night could be due to excessive NE firing, which is why these drugs ___________ are sometimes used to treat anxiety and nightmares.

Answer 11

blood pressure drugs

Question 12

There’s a parabolic curve showing the effects of too little and too much of the neurotransmitters that regulate wakefulness.

Answer 12

too low wakefulness NTs –> sleepiness
too high wakefulness NTs –> insomnia, anxious

there’s an optimal level of NTs to maintain optimal activity.

Question 13

What secretes the wakefulness neurotransmitter, histamine? What happens when histamine binds H1 receptors. What are H3 autoreceptors?

Answer 13

Tuberomammilar nucleus in posterior hypothalamus secretes histamine

• histamine + H1 receptors –> wakefulness
• H3 autoreceptors will inhibit histamine so antagonize H3 receptors –> wakefulness

Question 14

Dorse raphe nucleus secretes serotonin. Serotonin promotes wakefulness & inhibits REM. Serotonin can promote wakefulness by binding to which markers? Drugs that block which serotonin receptor can promote & correct circadian rhythms? Drugs that block which serotonin receptors can promote NREM?

Answer 14

• Serotonin + 5-HT-1a, 5-HT-1b, 5-HT2, 5-HT3 –> wakefulness
• drugs that block 5-HT2 –> promote NREM
• drugs that block 5-HT7 promote & correct circadian rhythms

Question 15

Dopamine is a reward chemical, and is also a wakefulness NT. What 3 areas secrete dopamine?

Answer 15

• substantia nigra
• ventral tegmental area (VTA)
• ventral PAG

Question 16

Orexin/hypocretin is not part of reticular system. What does it do?

Answer 16

It is a backup generator to keep other neurotransmitters functioning to maintain wakefulness. Hence, these neurons innervate other wakefulness areas (LC, TMN). This backup generator only fires during wakefulness.

Question 17

On the EEG, when do you see spindles? Where do these sleep spindles originate?

Answer 17

Spindles are seen in stage 2 of NREM sleep recorded by EEG. Spindles originate in the thalamus. NREM thalamic neurons are hyperpolarized & decrease responsiveness to external stimuli

Question 18

The thalamus uses glutamatergic neurons & GABAergic neurons to affect ascending arousal pathways. What are the effects of glutamate & GABA on wakefulness?

Answer 18

• glutamate –> arousal, wakefulness

- GABA –> dampen ascending arousal pathways to induce sleepiness

Question 19

What is the SCN?

Answer 19

The suprachiasmatic nucleus (SCN) governs the 24 hr sleep wake clock as the internal biological clock and is located in hypothalamus.

Question 20

There are 3 parts (The Dimmer, The Simple Switch, and the Backup generator) that play a role in the anatomy of being awake. Briefly explain them. Patients who present with problems with wakefulness and/or sleepiness can have drugs to manipulate these different systems (the Dimmer, the Simple Switch, and the Backup generator).

Answer 20

1) The Dimmer -Reticular Activating System
- operates by incrementally increaseing NE, DA, SR, ACh (go from 0 - 150%)

2) The Simple Switch -TMN & VLPO
- operates in bipolar, all or none fashion by facilitating histamine or GABA (either 0 or 100%)

3) The Back up generator -Orexin/Hypocretin System
- operates by incrementally increasing orexin (go from 0 to 100%)
- innervates the Dimmer & the Simple Switch

Question 21

Defects in the back-up generator can cause what clinical condition?

Answer 21

Narcolepsy