How does the brain control sleep and wake?

Nina Vujovic

Program in NeuroscienceHarvard Graduate School of Arts and Sciences

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The human brain

Kimberly Kaminski

Wikimedia commons

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How do neurons communicate?

Images from: Wikimedia commons

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The cerebral cortex and consciousness

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Signals from deep brain to cortex keeps us alertIn brown aredopaminergicprojections to the cerebral cortex.

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A cluster of vital arousal-promoting neurons

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A cluster of vital arousal-promoting neuronsIn yellow arehistaminergric projections tothe cerebralcortex. Anti-histamines,found in someallergy medications,make you drowsy becausethey block thissignal.

X

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What if the arousal-promoting signal is disrupted?

lethargic, sleepy patients or animals

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How does the brain promote sleep ?

Ventrolateral pre-optic area(VLPO)

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What if the sleep-promoting VLPO signal is disrupted?

• Aging leads to VLPO neuron loss– Problems sleeping more common among elderly

http://lua.weblog.com.pt/CAFFEINE.JPG

• Animals with VLPO injuries sleep only 50% as much as normal animals

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Sleep - Wake Transitions

• We don’t spend much time in drowsy in-between states

• But what keeps us from flipping back and forth between sleep and wake all the time?

Sleep-promoting VLPO

wake-promoting system

vs.

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How do we STAY awake?

orexin neurons

(they keep you from havingnarcolepsy)

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What governs timing of sleep?• Energy regulation system

• Circadian timing system

Reset with light

Recharge with sleep

Quick fix:

+

-

A P P P

Runs with near 24-hour period

Does this even in the absence of light cycle

P P P

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Adenosine tri-phospate Adenosine binds to neuronsand makes us feel tired. Caffeine blocks this interaction, actingto trick our brain into thinkingwe are not tired.

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The circadian timing system tells what time it is via light

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Four major ways to mess with sleep

1. Forced schedule that goes against circadian and energy regulation systems

2. Injury to neurons that regulate sleep

3. Drugs that mimic neurotransmitters

4. Unusual circumstances

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Unusual circumstances:• Unusual or uncomfortable environment

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Unusual circumstances:• Unusual or uncomfortable environment• Low oxygen/high CO2/breathing problems

Zzzzz ZzZZZZ <gasp>

* *

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Unusual circumstances:• Unusual or uncomfortable environment• Low oxygen/high CO2/breathing problems• Inner ear issues/zero gravity

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Unusual circumstances:• Unusual or uncomfortable environment• Low oxygen/high CO2/breathing problems• Inner ear issues/zero gravity• Gastrointestinal/urological problems

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Unusual circumstances:• Unusual or uncomfortable environment• Low oxygen/high CO2/breathing problems• Inner ear issues/zero gravity• Gastrointestinal/urological problems• Severe hunger, pain or stress

Owww!

ooof…

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Summary

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• deep brain arousal-promoting neurons stimulate cortex to promote wakefulness

• VLPO inhibits these neurons to promote sleep• orexin neurons help consolidate wakefulness• circadian and energy regulation systems govern timing

and duration of sleep• unusual circumstances, brain injuries, or drugs can

override VLPO signal and disrupt sleep• understanding these systems better may lead to new

treatment or prevention options for sleep disorders

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Thank you!

http://healthysleep.med.harvard.edu/portal/

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