W7L2 - Function of Sleep (2)

Question 1

Broad evidences for sleep for body restoration

Answer 1

1. Exercise
2. Physical Injury
3. Immune Function

Question 2

Sleep for Body Restoration: Exercise

Answer 2

• Acute exercise has minimal effect on sleep
• Severe exercise can negatively impact sleep.

Question 3

Sleep for Body Restoration: Physical Injury

Answer 3

• Physical injury increases sleepiness,
• but medications, inflammation etc may contribute.

Question 4

Sleep for Body Restoration: Immune Function

Answer 4

Immune Function

• Immune function reduced when sleep deprived
  
  • 165 people exposed to common cold virus after a week of actigraphy to assess sleep: negative association between virus and sleep duration
• Fever (to fight infection) impaired when sleep deprived
  *

Question 5

Evidences for Sleep for Brain Restoration

Answer 5

1. ) Glymphatic System
2. ) Synaptic Homeostasis Hypothesis (SHY)
3. ) Neural Network Theory

Question 6

What is Glymphatic system and its function

Answer 6

Glymphatic system

• Pathway of fluid flow in the brain

Function

• Clearance of macroscopic waste
• Ensures even distribution of macromolecules throughout the brain (glucose, lipids, amino acids, growth hormone)

Question 7

Explain CSF liquid flow in the brain and its link to glymphatic system.

Answer 7

• CSF and interstitial fluid continuously interchange.
• Waste products are collected from the interstitial space and exit the brain via the glymphatic system.

Question 8

Glympahtic system in sleep: Explain

Answer 8

Glymphatic flow dramatically increased in sleep.

Awake

• Astrocytes are big
• Not much interstitial space > lack of fluid flow > Metabolite accumulates

Asleep

• Astrocytes shrink
• 60% more interstital space > Increased convective flow > Augmented metabolite clearance

Question 9

Experiment: Gymphatic System and the link to AD

Answer 9

Expriment

• In exprimental rates, they manipulated astrocyte size
  
  • Beta-amyloid builds up and forms plaques (as in AD)
  • 65% of the brains beta amyloid is removed through the glymphatic system during sleep.

AD

• Beta-aymloid causes AD
• Sleep problems are a common complaint in AD and poor sleep increases the risk of developing AD (particularly in genetically predisposed people)

Question 10

Evidences for sleep involved in consolidating memories?

Answer 10

Walker (2004)

• Motor Task
  
  • Dramatic improvement after sleep
• Visual Skill Task
  
  • Sleep after learning the task is crucial

Question 11

What is the complexity of sleep-memory relationship

Answer 11

• Very few studies look at memory encoding in the presence of sleep deprivation
  
  • only consolidation
• Different memory types
  
  • ​declarative, etc…
• Different components of sleep
  
  • REM, NREM

Question 12

What is relationship between learning and memory at a cellular level?

Answer 12

Learning and Memory occur via changes in

• Neuronal firing
  
  • (increased) neuronal firing of connections that already exist
• Neuronal connections
  
  • (New) Neuronal connections

Question 13

What is Synaptic Homeostasis Hypothesis (SHY)

Answer 13

SHY: Sleep is Synaptic Downscaling

• Wakefulness is associated with synaptic potentiation in cortical circuits.
  
  • Net increase in synaptic weight
  • Energy and space costs
  • Changes are use dependent

Question 14

How is synaptic weight reflected?

Answer 14

• Synaptic weight is reflected in the amplitude of EEG waves and thus SWA (Synchronous firing)
• Synaptic down scaling is a consequence of SWA, thus the exponential fall in SWA (SWA falls over the night)

Question 15

SHY: Implications for Learning and Memory

Answer 15

• If synaptic changes occur during wakefulness, any change in relative strength of a connection is present prior to sleep
  
  • No improvment after sleep
• It may also improve the signal to noise ratio, but only if synapses are lost when their strength falls below a threshold
  
  • Losing irrelevant information
• Synaptic down scaling may be of benefit by creating “space” for new learning

Question 16

3 Evidence in support of SHY

Answer 16

• Genes involved in synaptic plasticity (LTP) are upregulated in wakefulness.
• Structural evidence in Drosophila show the expected synaptic size/number changes during wake/sleep
  
  • More simplistic structure (Downscaling)
• Resting firing rate of neurons are increased in wake or sleep deprivation, reduced after sleep.

Question 17

SHY suggests SWA should increase in different parts of the brain in a use dependent fashion (non-uniform across the brain). 1st Experiment examining this issue: Methods

Answer 17

Vyazovskiy et al. (2000)

Unilateral sensory stimulation during wakefulness in rats

• Cut whiskers on one side
  
  • Reduce input to contralateral cortex
• Rats then spend 6 hours in an enriched environment
• Measured cortical activity (EEG) in the subsequent sleep period and compare SWA in the two hemispheres

Question 18

SHY suggests SWA should increase in different parts of the brain in a use dependent fashion (non-uniform across the brain). 1st Experiment examining this issue: Results and Conclusion

Answer 18

Results

• SWA relatively Higher in Hemisphere contra-lateral to intact whiskers

Conclusion

• SWS sleep may occur as a local response to the activation of a brain region

Question 19

SHY suggests SWA should increase in different parts of the brain in a use dependent fashion (non-uniform across the brain). 2nd Experiment examining this issue: Methods

Answer 19

Huber et al. (2004)

• (Easy vs Hard) Motor learning task and EEG sleep

Question 20

SHY suggests SWA should increase in different parts of the brain in a use dependent fashion (non-uniform across the brain). 2nd Experiment examining this issue: Results and Conclusion

Answer 20

Results

• General sleep architecture was the same in the two conditions
• But when SWA distribution in the two conditions were specifically compared, the hard condition produced a local increase in SWA in the right parietal region.

Question 21

What is neural network theory?

Answer 21

• Sleep is initiated at a local level in response to local brain activity, rather than being imposed by sleep regulatory networks
  
  • Arose out of the observation of the existence of cortical columns.

Question 22

What are Cortical Columns

Answer 22

• Collections of highly inter-connected neurons that often focus on particular tasks. There is more intercellular connectivity within columns than between columns, making each column a functional unit
  
  • 1,000 to 10,000 cells per column
  • About 100,000 columns

Question 23

What is sleep-wake state correspondence between cortical columns

Answer 23

• Seep should occur in these columns more strongly/independent of other columns.

Question 24

Evidence for sleep at local level (from epilepsy studies)

Answer 24

• Implanted EEG electrodes in epilepsy
• Different areas of the brain can simultaneously be in different states.

Question 25

Anecdotal Evidence for Local Sleep

Answer 25

• Sleep Disorders:
  
  • Sleep walking and talking
• Marine mammals (hemispheric sleep)
• Normal sleep unfolds regionally
• Amount of SWS is regionally use dependent
• Local sleep may also explain sleep phenomena such as sleep inertia and performance lapses during prolonged wake.

Question 26

How is Global Sleep achieved if the neural network theory is correct?

Answer 26

• Use dependent local sleep:
  
  • Local homeostatic demand drives local sleep processes. How is it that the brain tends to act in concert?
    
    • Parallel independent processes have almost same homeostatic drive.
      
      • Baseline activity builds up at about the same rate – so they all fall asleep at the same time
    • Sleep may be “contagious” between cortical columns.
    • Independent processes entrain each other.