Brain mechanisms that control sleep and waking

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Brain mechanisms that control sleep and waking

• Jerome Siegel
• By group 2

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Electroencephalogram

• Developed by Hans Berger in Jena, Germany
• Records the electrical activity of the brain and
  provides objective measure of the state of the
  brain, and states of consciousness
• Bergers work showed clear signs of sleep in 2
  categories REM and NREM
• Awake EEG characterized by low voltage (5-50 muV)
  and high frequency (20-40 Hz)

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Stages of sleep (EEG cont)

• Sleep stage 1 EEG resembles waking state,
  transitional state
• Stage 2 and 3 characterized by sleep spindles
• Stage four has the highest amplitude and lowest
  frequencies
• Each cycle of Non-REM sleep is followed by a REM
  episode 90 min and 5 sleep cycles in 8 hour
  sleep period

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Stereotaxic instrument

• Developed by Victor Horsley and Robert Clark in
  London
• Head is fixed in standard orientation
• Atlas of brain with plates used to position the
  probe
• Permits probes to be inserted into the brain
  experimentally to manipulate deep structures

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Cathode Ray Oscilloscope

• Necessary to explore the electrical activity of
  the brain at the single cell level
• Has virtually no inertia, can respond with
  millisecond, and submillisecond speed
• Permitted discovery of neural events at the
  cellular level that occur during waking and sleep

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Encephalitis Lethargica

• During 1917-1919 world wide influenza epidemic,
  Spanish flu
• Variant of the disease that cause sleep coma
• Discovered by Constantin von Economo using a
  stain selective to cell bodies revealed profound
  loss of cells in posterior hypothalamus and
  adjacent regions of mesencephalic reticular
  formation
• First evidence these structures were necessary in
  waking state
• Inability to sleep (insomnia?) loss of cells in
  anterior hypothalamus and adjacent preoptic area
  of basal forebrain (these areas critical for
  ability to sleep)

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Encephalitis Lethargica

• Areas important for waking
• - Posterior hypothalamus
• - Anterior reticular formation
• Areas important for sleep
• - Anterior hypothalamus
• - Preoptic area

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Neural Structures and pathways for arousal

• Moruzzi and Magoun
• Electrically stimulated the mesencephalic
  reticular formation of cats when EEG signified a
  sleep-like state
• Upon stimulation onset rapid and dramatic change
  of EEG
• Destruction to the area stimulated, produced
  animals with sleep like behavior and EEGs
• Due to the findings, the reticular formation
  became known as the ascending reticular
  activating system (ARAS)

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Pathways for arousal

• Brachium Conjunctivum a prominent fiber tract
  that goes through the pontine and mesencephalic
  brain stem
• Surrounding it are two nuclei (collectively known
  as the Peribrachial Nuclei)
• Pedunculopontine Tegmental Nucleus (PPT)
• Erodorsal Tegmental Nucleus (LDT)
• This nuclei contain acetylcholine-synthesizing
  neurons

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Sagittal view of cholinergic pathways of rat
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Dorsal and Ventral Pathways

• These two pathways mediate cortical arousal from
  activation to the peribrachial nuclei
• Dorsal Direct peribrachial cells --gt midline
  intralaminar nuclei of the thalamus--gt broad
  areas of cortex
• Glutamatergic projections from thalamus

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Ventral Pathway

• Complex route, prior to thalamus, components
  course through ventral region of forebrain, or
  hypothalamus
• Hypothalamic cells of the nucleus release
  histamine which produces strong arousal on the
  cerebral cortex
• The neurotransmitter used to activate cortex are
  GLU, histamine, hypocretin and ACh

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Neural control of NREM Sleep

• Siegel and colleagues
• Showed sleep inducing stimulation produced EEG
  slow wave while at the same time producing a
  firing pattern of cells in brain stem ARAS
  (decreased firing)
• Finding suggest that sleep inducing influence has
  its effect by inhibiting the neural activity of
  the ARAS

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NREM and Basal forebrain area

• Involved in producing arousal
• Stimulation in cats produced EEG and behavioral
  signs of sleep
• Cholinergic cells that project to cortex mediate
  the basal forebrain producing arousal
• Sleep inducing effect of the basal forebrain is
  mediated by inhibitory effect of GABA on
  hypothalamic component or ARAS
• Without Basal Forebrain inhibitory influence, the
  histaminergic arousal system stays active which
  leags to inability to sleep (insomnia)

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Neural control of REM Sleep

• 1953 Aserinsky and Kleitman
• Studied dream sleep
• During episodes of dream sleep there are Rapid
  Eye movements, and the EEG reflects that of an
  awake brain
• REM episodes occur in all mammalian species
  investigated and is sometimes seen in other
  vertebrates
• In addition to eye movements and EEG recordings
  of an awake-like state, there are autonomic
  changes as well
• Irregular heart rate
• Increased blood pressure
• Increased pupil diameter

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REM sleep

• Males show penile erection (sorry folks no
  picture available)
• Women show comparable signs of sexual arousal
• There are spike like transient waves from pons
  area, LGN, thalamus, and occipital cortex
  (referred to as PGO waves
• Electrodes close to the hippocampus show theta
  waves
• Non-autonomic changes of REM
• Muscle tonus in straited skeletal muscle abolished

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• The fast activity EEG recordings from the cortex
  reflect a cognitively active brain dream state
• The sympathetic arousal possibly prevents the
  dreams from being acted out
• However, it is unknown why there are theta waves
  from the hippocampal area
• The cholinergic peribrachial nuclei at the
  pontine-mesencephalic junction is activated
  during REM
• Since the dream state is emotionally charged, the
  ventral pathway which interacts with the
  hypothalamus and other limbic areas are activated
  during REM

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• When there is a lesion to the nucleus
  subcoeruleus of the dorsal pons, REM sleep
  paralysis becomes abolished
• Cats with lesions to the area become very
  agitated during REM sleep, as if acting out the
  dream
• REM onset and offset controlled circuits between
  the pons and medulla
• Also may be due to activity of cholinergic cells
  of the peribrachial nuclei and the mesopontine
  brain stem

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Function of Sleep

• Approach most widely used to explore functions of
  sleep sleep deprivation
• Evidence from studies suggest sleep serves at
  least two functions
• Keep the immune system functioning properly
• Facilitation of memory consolidation

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Function of Sleep

• When fruit flies are prevented from resting, then
  allowed to rest, will show an increased amount of
  time in this quite state
• Suggests sleep is programmed homeostatic process
  that regulates time for sleep in insects and in
  humans
• It has proven difficult to selectively deprive
  subjects of slow-wave sleep and REM because REM
  only follows NREM slow-wave sleep

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Function of Sleep

• In the late 1980s Rechtschaffen and colleagues
  showed that depriving rats from sleep for 2-3
  weeks would kill them
• They were also able to selectively deprive rats
  of REM sleep and it took 3-4 weeks for them to
  die (how nice!)
• Two of the most important changes that occurred
  during sleep deprivation of the rats were
  increased food intake (up 80-100) while
  simultaneously showing significant weight loss

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Function of Sleep

• The second change, which was said to be the
  ultimate cause of death, was bacterial infection
• The rats were highly susceptible to illness
  because sleep deprivation left their immune
  systems unable to fight incoming invaders
  (Everson and Toth 2000)
• There is some debate whether the cause of
  dysfunctional immune system was due to sleep dep.
  or stress.

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Function of Sleep

• Effects of sleep deprivation are not as severe
  for humans
• After receiving vaccinations for hepatitis and
  influenza, human subjects who were deprived of
  sleep showed a reduction in the anti-bodies that
  protect against diseases.
• However, Siegel neglected to include how subjects
  were deprived from sleep and for how long.

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Function of Sleep

• Other studies suggest sleep is important for
  memory consolidation
• Experiments have shown that subjects who are
  trained to perform a certain task and then
  allowed to sleep show better performance than
  subjects who are not permitted to sleep
• Hennevin and Colleagues found learning of
  subjects would show small daily improvements, and
  then on a particular day would show drastic
  improvement

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Function of Sleep

• Hennevin and Colleagues also found performance
  was drastically improved immediately following
  REM sleep
• This data led Hennevin and Colleagues to propose
  that REM sleep is important for larger amounts of
  memory processing

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Function of Sleep

• Another fascinating study was conducted by
  Stickgold and colleagues in 2000 that found
  subjects showed no improved performance unless
  they were allowed to sleep within 30 hours of
  training
• Stickgold and colleagues provided data to support
  the hypothesis that slow-wave sleep and REM sleep
  towards the morning are vital for the
  consolidation of memory

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Lucid dreaming

• http//video.google.com/videoplay?docid-970430747
  23881963qwakinglife2Bluciddreamtotal54st
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