Lecture 8: Sleeping

Question 1

What is a circadian rhythm? Infradian? Ultradian?

Answer 1

24 hour cycles, longer than a day (shorter than a year), ultradian (shorter than a day).

Question 2

Name 5 examples of biorhythms:

Answer 2

1. core body temp
2. urine volume
3. melatonin
4. cortisol
5. growth hormone

Question 3

How do we know that light is not behind circadian rhythms?

Answer 3

Wheel-running behavior shows periodic variation in rodents throughout the day. Also, nocturnal rodents run more at night.

Question 4

What are internal biorhythms? How do we know they exist?

Answer 4

Rhythmic cycles that exist without light. They are endogenous to organisms. When humans are placed in a bunker and could control when lights are on-off the sleep-wake cycle shifted from 24 to 25-27 hours.

Question 5

What are zeitgebers?

Answer 5

Time givers, for example clocks. When light cues are delivered at bad times, different from our zeitgebers, our normal rhythms are disrupted (i.e., jet leg, light pollution).

Question 6

How does our body get entrained to light?

Answer 6

1-3% of retinal ganglion cells (RGCs) express a light sensitive pigment (melanopsin) which is sensitive to blue light and always sends the signals if they are received. This signal is sent to the retinohypothalamic tract which leads to the hypothalamus (to the super charistmatic nucleus, SCN).This is right above the optic chiasm where the pathway dessucates to other areas of the brain. This signal entrains shell neurons.

Question 7

What does a SCN lesion lead to?

Answer 7

The abolishment of many circadian rhythms.

Question 8

What do we see in the SCN during the day of diurnal animals?

Answer 8

More activity, maintain rhythmic activity even when deprived of input (tracts being removed).

Question 9

How do SCN cells maintain their activity w/o input?

Answer 9

Because neurons in the SCN have rhythms of gene expression called period genes.

Question 10

What are the three period genes in the SCN?

Answer 10

1. Cryptochrome genes (CRY1 and CRY2)
2. Clock Protein
3. BMAL Protein

Question 11

What was the CRY1 gene associated with?

Answer 11

Delayed sleep phase disorder (a condition where you got to bed and rise later than socially appropriate)

Question 12

Where does melatonin production happen? What is it inhibited by? What is its role?

Answer 12

Pineal gland. Light. Plays a role in sexual maturity. In the winter there is less light so more melatonin, smaller gonad size. Evolutionarily adaptive.

Question 13

Where does cortisol production happen?

Answer 13

Paraventricular nucleus (PVN)

Question 14

What rises first before waking, melatonin on cortisol?

Answer 14

melatonin.

Question 15

What is the effect of exercise on biorhythms?

Answer 15

The dorsal raphe (DRN) + median raphe (MRN) mediate the influence of exercise on SCN activity. Results in strengthened biorhythms.

Question 16

What are two conditions where you get a phase advance?

Answer 16

1. Daylight earlier

2. Exercising early

Question 17

What is the reticular activating system (RAS)?

Answer 17

It is sensitive to sensory input. It stimulates reticular formation which promotes arousal. It is connected to the basal forebrain which sends cholinergic inputs to the rest of the brain (choline). Coma can occur with injury to the dorsal pontine reticular formation.

Question 18

How do we know what the RAS does?

Answer 18

1. Damage to the RAS or its input channels to higher brain centers, we see an EEG similar to sleep.
2. When you stimulate this area during sleep, the animal wakes up.
3. When you cut off brain stem input to the RAS you would not affect the rhythmicity of the EEG.
4. Cat slide?

Question 19

Why do we need sleep? (6)

Answer 19

1. Maintenance of brain
2. Restoration of injured tissue
3. Ontogenetic development of the brain
4. Maintenance of learning + memory processes
5. Energetically favorable
6. Dreaming

Question 20

What is meant by the maintenance of the brain? (3)

Answer 20

1. Certain metabolites are best cleaned during sleep (i.e., Alzheimer’s is when this doesn’t happen)
2. More sleep is associated with better memory and cognitive performance (memory consolidation)
3. Neural networks formed during sleep which lay a foundation for future learning.

Question 21

What happens in the HC during sleep after a spatial task?

Answer 21

Cells in the hippocampus that were involved in the task become linked (show correlative activity) during NREM sleep (evidence from rodents and humans).

Question 22

What happens in the motor cortex during sleep after a motor task?

Answer 22

In humans, neurons involved in executing an implicit motor task may again become active during sleep (similar but not identical pattern of activity).

Question 23

What is pre-play?

Answer 23

During sleep, neural networks are built to store future memories (e.g. like humans, neurons involved in executing an implicit motor task may again become active during sleep (similar but not identical pattern of activity).

Question 24

Describe the sleep stages and their EEG signatures?

Answer 24

1. Awake: Beta >13 Hz
2. Drowsy: Alpha 7-13 Hz
3. Stage N1 sleep (NREM1 - light sleep): Theta 4-7 Hz (alpha + theta)
4. Stage N2 sleep: sleep spindles (theta) with spindles and K-complexes
5. Stage N3: Delta 1-4 Hz (deep sleep or slow wave sleep, some spindles), efficient sleepers (<6 hours) spend more time in NREM3
6. REM (Dream Stage): fast and random (activity is similar to wakefulness)

Question 25

What's the difference between the sleep signatures of children vs older adults?

Answer 25

Young children: most sleep is REM. Older adults, less REM, less deep sleep, greater sleep latency, more arousal periods (awakenings), less REM, less NREM3, less sleep overall.

Question 26

What is atonia and when does it happen?

Answer 26

Atonia is lack of muscle tone produced by the subcoerulear nucleus exciting the magnocellular nucleus of the medulla which inhibits spinal motor neurons.

Question 27

What are REM related activities?

Answer 27

Neocortex activated by basal forebrain nuclei. Excited brainstem nuclei produce REM and other twitching movements.

Question 28

What does REM deprivation lead to?

Answer 28

Lack of REM is associated with reduced hippocampal neurogenesis, immune dysfunction and mood disruption (suppression of REM occurs with antidepressants which improve mood).

Question 29

What happened when you replaced REM states with wakeful states?

Answer 29

Prevented REM rebound which is an increased amount of sleep a person received as a result of being sleep deprived or stressed during waking hours.

Question 30

What are the theories for dreaming? (3)

Answer 30

1. Theory of wish fulfillment (act out repressed desires - Freud) 2. Activation-Synthesis Theory (dream states an attempt by the brain to interpret random activity) 3. Evolutionary theory (dreams include events that are a threat to reproductive success, we devise new ways to manage these threats)

Question 31

What are the types of objective methods to study sleep?

Answer 31

1. Physiology during sleep, neurological activity during sleep (using EEG = electrical activity, EMG = breathing activity, EOG = eye movement) 2. Actigraphy: the actigraph measures sleep-wake times and can be used to verify a sleep diary (no technician needed)

Question 32

What are the types of subjective methods to study sleep?

Answer 32

Asking patients about their sleep patterns (self-report and questionnaires. First and necessary step that relies upon honest and accurate reports by patient.

Question 33

What are the types of subjective reports?

Answer 33

1. Athens Insomnia Scale 2. Pittsburgh Sleep Quality Index 3. Insomnia Severity Index

Question 34

What is the DEC gene mutation associated with?

Answer 34

Associated with less sleep (slept 4-5 hours a day) | Mice w/similar DEC2 gene mutations sleep less.

Question 35

What is a quantitative trait?

Answer 35

A trait modulated by many genes.

Question 36

What is a chronotype?

Answer 36

Sleep schedule. | As you grow up, your chronotype changes (by your 20s your chronotype moves back, you wake up earlier and earlier).

Question 37

Gender and age differences in chronotypes?

Answer 37

Men are more likely to have a later chronotype (wake up later). From child - 20, your chronotype moves forward.

Question 38

Why is GPA negatively correlated with dim-light melatonin onset?

Answer 38

Low amounts of melatonin = low sleep pressure. The higher your GPA, the lower the dim-light melatonin.

Question 39

What are short/long term effects of sleep disruption?

Answer 39

Short term: Stress, somatic, psychological issues. Long-term consequences: cardiovascular disease, obesity, T2DM, Cancer, Death Check out the physiological effects

Question 40

What are sleep problems associated with?

Answer 40

Associated with impairments in motivation and attention (more than cognition) Associated with weight gain and immune dysfunction.

Question 41

What happens during exam season?

Answer 41

Less sleep, more cortisol, self-report of stress is higher (but overreporting based on cortisol).

Question 42

What is insomnia?

Answer 42

Difficulty falling asleep or staying asleep. Can be acute or chronic, and may reoccur. Primary insomnia is rare (~10% of cases) whereas secondary/comorbid insomnia (90%) common. Insomnia is commonly comorbid with neuropsychiatric disorders such as depression and anxiety (33% of all insomnia is linked to these two disorders).

Question 43

What is cataplexy?

Answer 43

Loss of motor control (atonia) without loss of consciousness Triggered by arousing stimuli (e.g. laughing, crying, terror, running) Common in narcolepsy (70% of cases).

Question 44

How does cataplexy happen?

Answer 44

Atonia is caused when specialized neurons inhibit motor neurons These neurons are inhibited by orexin-expressing neurons in the lateral hypothalamus. Loss of OX neurons leads to increased activity of the specialized cells which inhibit motor neurons + atonia. Immuno activity destroys these OX neurons. Supplementing with orexin can help (restores normal behavior).

Question 45

What is narcolepsy?

Answer 45

Characterized by extreme daytime sleepiness (tested by waking people up during sleep to see how fast REM sleep happens) Rapid descent into REM sleep is common. The disorder is treated with amphetamine or GABA agonists or orexin/hypocretin peptides (to mimic the signaling compounds that have been lost).

Question 46

What is somnambulism?

Answer 46

A disorder in which the person leaves the bed an moved around More common in childhood (~12 years), only 4% of adults experience it There have been reports of complex, aggressive and illegal behaviors while sleepwalking Somnambulism occurs during NREM but not REM.