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Today’s topic: Functions of Sleep in Humans and the Animal Kingdom
Speaker: Dr. Addo Boafo
child & youth
Mental Health Series
Date
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Declaration of conflict
Speaker has nothing to disclose with regard to commercial support.
Speaker does not plan to discuss unlabeled/ investigational uses of commercial product.
Acknowledgments
Chloe Stevens, Bachelor of Health Science at Carleton
University, CHEO volunteer
Objectives
1) To learn about how to define and measure sleep
2) To learn about the Neuronal Group Theory of Sleep
3) To learn about six of the presumed functions of sleep
Defining and Measuring Sleep Across the
Animal Kingdom
Behavioural
Electrophysiological
Molecular
Metabolic
Neurotransmitter
Six Criteria of Sleep (Flanigan, 1973)
1. Preferred posture
2. Behavioural quiescence
3. Rapid state reversibility
4. Decreased responsiveness to surroundings (elevated
arousal threshold)
5. Homeostatic regulation (Campbell & Tobler, 1984):
rebound with increased sleep intensity or duration after
sleep loss
6. Electrical changes in brain’s activity in sleep
Behavioural and
Electrophysiological
Findings
Mammals
a) Electrophysiology
b) Neurotransmitters
c) Hormones
(Rasch & Born, 2013)
Molecular Manifestations of Sleep
The following are gene expressions increased during
wakefulness (Collingridge, Issac, & YWang, 2004, in Hinard
et al., 2012):
a) Immediate Early Genes (IEG) such as Homer (an expression gene),
Arc, Dbp and others, as well as genes expressing glucose
metabolism, lipid metabolism, cell cycle inhibitors (for example
apoptosis)
b) Plasticity-related gene expressions (and increased trafficking and
phosphorylation of postsynaptic glutamatergic AMPA receptors
containing GluRI subunit)
Metabolic Manifestations of Sleep
The following are increased during wakefulness (Hinard et
al., 2012):
a) Oxygen consumption
b) Glucose consumption
c) Metabolites (by-products) such as Alanine and Lactate (by-
product of glycolysis); Lysolipids (reflect membrane breakdown)
Neurotransmitter/Hormonal Manifestations
of Sleep
(Joiner, 2016)
Where Does Sleep Begin?
Central Nervous System
Individual Neuron
Group/Network of Neurons
Whole Brain
Half Brain
Local areas of Central Nervous System
Findings Supporting the Neuronal Group
Theory of Sleep
a) Whales, dolphins, migrating birds
b) Human traumatic brain injuries, strokes, etc.
c) Local sleep in awake rats (Vladyslav, 2011)
d) C. elegans (a worm, 1 mm long)
e) Neurons grown in the lab
C. elegans
1 mm in length
302 neurons
No complex structures such
as brain
Anatomy of a Neuron
Nucleus
Axon
Dendrites
Synapses
Synaptic cleft
Myelin sheath
Two Neuron Network
Glial cells outnumber
neurons 3:1
Glial cells start out as
precursor cells
Example of Neurons Grown in a Lab
(Hinard et al., 2012)
Functions of Sleep
There are several questions, for example:
a) Why do we need to sleep?
b) Why do some animals sleep at night and others during the day?
c) Why the “zoning out”/ relatively unconscious state?
d) Why does the armadillo sleep 20 hour and the wild African
elephant matriarch only 2 hours?
e) Does sleep exist to serve single neurons, a network/group of
neurons, the whole brain, whole body – do other organs or
structures such as the liver and kidney sleep?
Functions of Sleep
“Press reset button”
“Boost memory consolidation”
“Boost memory of immune system”
“Energy conservation”
“Sweep and Clean up the garbage”
“Service and Repair wear and tear”
Synaptic Homeostasis
(Wolf et al., 2016)
Activity at Synaptic Cleft
(Electrical/Chemical)
(Kruger et al., 2016)
Synaptic Homeostasis – Long-term
Potentiation
Persistent increase in synaptic strength following high
frequency stimulation of chemical synapse – product of:
1. Increase in number of release sites (increases synaptic strength)
2. Presynaptic release probability (increases synaptic strength)
3. Bigger (stronger) postsynaptic electrical response to release
transmitters (increases synaptic strength)
Sleep Boosts Memory Consolidation
Driven by Slow Wave Activity (less than 4 Hz)
Likely occurs early in sleep
Certain skills have the biggest boost – puzzle, piano/guitar
(Rasch & Born, 2013)
(Rasch & Born, 2013)
Sleep Improves Memory Forming Immune
Response
Boost likely if slow wave sleep is within 36 hours of
inoculation
Confirmed for Influenza and Hepatitis A and B inoculation
Adaptive Immunity
(Lange et al., 2011)
The Concept
Encoding: uptake of the antigen by APCs
Consolidation: two cell combo between APC and T helper
cell (immunological synapse); redistribution into long-
term storage
Recall: two cell types formed; B cells (produce antibodies)
and cytotoxic T cells work together to facilitate an
immune response upon reencounter of antigen
Hepatitis A and B virus, as well as influenza virus
(Lange et al., 2011)
Sleep Function - Energy Conservation
During sleep:
a) Reduction in energy expenditure of 7-69% among different
mammals (Toutain, Toutain, Webster, & McDonald, 1977)
b) Energy expenditure up by 7% in first 24 hours of sleep deprivation
c) Energy expenditure down by 5% during 8 hour recovery sleep
d) Energy expenditure up by 32% during sleep deprivation (Jung et
al., 2011)
Action Potentials
Human brain – 20-25% total body
energy expenditure
80% of brain energy used for
action potentials
Action potentials: electrical
currents generated by neurons
Human brain – 2% of total body
weight
Energy Conservation
Passive/Inactive Process (Berger & Phillips, 1995):
respiration rate, heart rate, gut motility, muscle activity
It is an active process (Schmidt, 2014) – Energy allocation
hypothesis
Energy Conservation - HydroOttawa
Model
Sleep Functions as Waste Management
System
Discovered in 2012 by Nedergaard
et al.
Components: as in image on right
Space between neurons increase
during sleep, allowing the brain
to flush out toxins that build up
during waking hours
Glia shrink during sleep
Sleep Functions as Waste Management
and Plumbing System
Increased circulation in mice CSF during sleep
60% increase in interstitial space
95% decrease in tracer activity during waking hours
2015, in mice posture lateral more than supine
(Xie, 2013)
Sleep Functions – Maintenance and
Repairs
Repair of neurons (Bellesi et al., 2013)
Repair of DNA (Bellesi et al., 2016)
Gene (DNA) Damage
Summary of the Functions of Sleep
“Press reset button”
“Boost memory consolidation”
“Boost memory of immune system”
“Energy conservation”
“Sweep and Clean up the garbage”
“Service and Repair wear and tear”
Practical Applications and Comments
Inoculations (flu)
Exams: piano or guitar
Alzheimer factor (amyloid-beta)
On-call physicians and local sleep phenomenon
Sleep deprivation relieves depression (temporarily)
Citations
1. Bellesi, M., Bushey, D., Chini, M., Tononi, G., & Cirelli, C. (2016). Contribution of sleep to the repair of neuronal DNA double-strand breaks: evidence from flies and mice. Scientific Reports, Rep 6: 36804, 1-13.
2. Bellesi, M., Pfister-Genskow, M., Maret, S., Keles, S., Tononi, G., & Cirelli, C. (2013). Effects of sleep and wake on Oligodendrocytes and their precursors. The Journal of Neuroscience, 33(36), 14288-14300.
3. Berger, R. J., & Phillips, N. H. (1995). Energy conservation and sleep. Behavioural Brain Research, 69, 65-73.
4. Campbell, S. S., & Tobler, I. (1984). Animal sleep: a review of sleep duration of across phylogeny. Neurosci. Biobehav. Rev, 8, 269-300.
5. Collingridge, G. I., Isaac, J. T.,YWang, Y. T. (2004). Receptor trafficking and synaptic plasticity. Nat Rev Neuroscience, 5, 952-962.
Citations
6. Flanigan Jr. W. G. (1973). Sleep and wakefulness in iguanid lizards. Ctenosaura pectinata and Iguana iguana. Brain, Behaviour and Evolution, 8, 401-436.
7. Hinard, V., Mikhail, C., Pradervand, S, Curie, T., Houtkooper, R. H., Auwerx, J. et al. (2012). Key Electrophysiological, Molecular, and Metabolic Signatures of Sleep and Wakefulness Revealed in Primary Cortical Cultures. The Journal of Neuroscience, 32(36), 12506-12517.
8. Joiner, W. J. (2016). Unraveling the Evolutionary Determinants of Sleep. Current Biology, 26(Oct. 24), R1073-R1087.
9. Kruger, J. M., Frank, M, G., Wisor, J. P., & Roy, S. (2016). Sleep function: Toward elucidating an enigma. Sleep Medicine Reviews, 28, 46-54.
10. Lange, T., Dimitrov, S., Bollinger, T., Diekelmann, S., & Born, J. (2011). Sleep after vaccination boosts immunological memory. Journal of Immunology, 187, 283-290.
11. Nedergaard, M. (2013). Garbage truck of the brain. Science. 340, 1529-1530.
Citations
12. Rasch, B., & Born, J. (2013). About sleep's role in memory. Physiological Review., 93, 682. 27
13. Schmidt, M. H. (2014). The energy allocation function of sleep: a unifying theory of sleep, torpor, and continuous wakefulness. Neuroscience and Biobehavioural Review, 47, 122-153.
14. Toutain, P. L., Toutain, C., Webster, A. J., & McDonald, J. D. (1977). Sleep and activity, age and fatness, and the energy expenditure of continued sleep. British Journal of Nutrition, 38, 445-454.
15. Vyazovskiy, V. V., Olcese, U., Hanlon, E. C., Nir, Y. Cirelli, C., & Tononi, G. (2011). Local sleep in awake rats. Nature, 472, 443-447.
16. Wolf, E., Kuhn, M., Normann, C., Mainberger, F., Maier, J. G., Maywald, S., et al. (2016). Synaptic plasticity model of therapeutic sleep deprivation in major depression. Sleep Medicine Reviews, 30, 53-62.
17. Xie, L., Kang, H., Xu, Q., Chen, M., Liao, Y., Thiyagarajan, M. et al. (2013). Sleep drives metabolite clearance from the adult brain. Science, 18(342), 1-11.
