L58 Sleep Flashcards
what are the functions of sleep?
- behavioral advantage
- maintenance
- maturation
- memory processing
- rest theory
what is the behavioral advantage of sleeping?
sleep protects us (with poor night vision) from predators
what is the maintenance function of sleep?
NREM sleep rests some neural circuits while REM sleep ensures activation of circuits
what is the maturation function of sleep?
REM sleep possibly involved in maturation of the nervous system
what is the memory processing function of sleep?
consolidation of short term memory to long term memory (good for passing exams)
what is the rest theory that is a function of sleep?
a necessary fall in neuronal activity and metabolic activity during NREM sleep
What are the different methods to study sleep?
EEG - with additional electrodes for heart rate, eye and body movements, respiration etc. (tells you about the cortical area)
PET, fMRI - to see changes in blood flow, metabolism
MEG - magnetoencephalography
EMG - electromyography
NCV - nerve conduction velocity
describe magnetoencephalography (MEG)
magnetic signals generated by neural activity
it localizes sources of neural activity better than EEG
it cannot provide detailed images like fMRI does…
what does the EEF record?
very small electrical fields generated by synaptic currents in PYRAMIDAL CELLS
records the synaptic activity of cortical neurons
describe desynchronized cortical activity and what type of brain is it associated with?
causes low (voltage) amplitude EEG waves normal awake brain
describe synchronized cortical activity and what type of brain is it associated with?
causes high amplitude EEG waves
sleeping brain
sleep is NOT a _____ physiological process
uniform
we have Day-night cycles
REM (paradoxical sleep) and NREM
what are the waves and EEG rhythms seen in sleep?
beta >12 Hz - activated cortex
alpha 8-12 Hz - quiet waking state
theta 4-8 Hz - some sleep states
delta 30 Hz - during wakefulness
what rhythms are seen when a person is awake with eyes closed?
alpha rhythm
what rhythms are seen when a person is awake with eyes open?
beta rhythm
what is the transition between alpha and beta rhythms in an awake person?
you will notice the blink artifact and that indicates when the eyes open
what rhythm is found in REM sleep?
Beta
what rhythm is found in stage 1 NREM sleep?
theta waves
what rhythms are found in stage 2 NREM sleep?
Spindle and K complex
what rhythms are found in stage 3 NREM?
delta
what rhythms are found in stage 4 NREM sleep?
delta
caused by inherent synchronous firing of cortical cells due to absence of sensory input + direct ARAS input
what is the normal sleep/wake cycle?
~90 min cycles
` 7 hours per night
**highly ordered structure
what stage of sleep is characterized by spindles and K complexes?
stage 2 NREM
define sleep spindle.
episodically appearing, spindle-shaped aggregate of 12-14 Hz waves with a duration of 0.5-1.5 seconds
identifies NREM stage 2 sleep
because of rhythmic firing of thalamocortical neurons due to decreased sensory and increase ARAS input
Define K complex.
sharp, negative, high voltage EEG wave, followed by a slower, positive component
it occurs spontaneously during NREM at the beginning and defining Stage 2 NREM
they can also be elicited during sleep by external (mostly auditory) stimuli
how much of total sleep time in a baby is REM
about half
how much of total sleep time in persons 15-75 years is REM?
about 20% of total sleep time
when is stage 4 NREM sleep maximum?
puberty
how much of total sleep does stage 4 NREM make up in early adulthood?
about 30%
how much of total sleep does stage 4 NREM make up in old age?
about 10% or less
the total about of time spent in sleep (REM and NREM) _____ with age
declines
when does REM sleep become more prominent?
towards morning
where is the biological clock located?
within the suprachiasmatic nucleus (SCN) in the anterior hypothalamus
each SCN neuron has about _____ hour cycle of activity
24-25
NO AP needed
Gene expression = Clock genes
how are the rhythms of the biological clock coordinated?
by the SCN based on light input from the outside world during daytime (excitatory input from retinal ganglion cells) and by influencing the activity of the pineal gland which secretes melatonin
define hypnogram
continuous graphical record of the different sleep stages showing the periods spent in each stage
what are the main CNS regions involved in the sleep-wake rhythm regulation?
nuclei in
-reitcular formation (in brainstem)
ascending - associated with consciousness
- thalamus
- hypothalamus
- basal forebrain
descending
-cerebellum sensory systems
define arousal
responsiveness of cortical and thalamic neurons to sensory stimuli (WAKEFULNESS)
describe the ascending arousal system
functional ground of neurons in the brainstem, thalamus, hypothalamus and basal forebrain that maintains and raises excitability in cerebral cortex
what is the brainstem part of the ascending arousal system often called?
ascending reticular activating system (ARAS)
what makes up the ARAS?
- thalamocortical transmission
- cholinergic structures
- monoaminergic structures - lateral hypothalamus, basal forebrain, and cerebral cortex
- NA, serotonin, histamine
- OREXIN/HYPOCRETIN***
- ACh, GABA
where is the ventral lateral pre-optic area/nuclei (VLPO) located and what is its function?
in hypothalamus (inhibitory GABA and galanin)
promotes sleep by inhibiting activity in the brain’s arousal centers
what happen when the activity of the ARAS pathways to basal forebrain are depressed?
onset of sleep
what happens when cholinergic cells are transiently activated during sleep?
onset of REM sleep
list the sleep promoting agents?
adenosine melatonin IL-1 muramyl peptides delta sleep inducing peptide eicosanoids (anti-inflammatory)
where is adenosine a sleep modulator?
at the synpase
what happens to adenosine concentrations in persons who are awake and sleeping?
awake - adenosine concentration increases which inhibits activity of ARAS
sleep - adenosine slowly decreases
when adenosine is administered = NREM sleep
when does melatonin concentration reach its max?
2-3am
when does melatonin concentration decline?
by 7 am
how is melatonin synthesized?
tryptophan –> serotonin –> melatonin
when is IL-1 produced?
during infections
when does IL-1 concentration increase in CSF?
during NREM sleep
IV injection of IL-1 = NREM sleep
describe how muramyl peptides promote sleep
its from bacterial cell walls
when injected into lateral ventricles of mammals = NREM sleep + fever and stimulation of immune system
when happens when Delta sleep inducing peptide is injected IV?
NREM sleep
when are pontine-geniculo-occipital (PGO) waves seen?
in periods of REM sleep when the EEG shows low amplitude and desynchronized (similar to that of awake state)
why does REM sleep kind of look like awake state?
pontine cholinergic cells fire in bursts = PGO waves
CN 3 is excited (REM/eye movements)
inhibition of most limb motor neurons
define the resistance to arousal in REM sleep
inhibition of transmission from the thalamus to the cerebral cortex in ALL specific sensory pathways (somatic, auditory).
define the muscular relaxation in REM sleep
neurons in the reticular formation inhibit the motor neurons in the spinal cord, mediated by those reticulospinal fibers, which use glycine as an inhibitory transmitter at the level of spinal cord.
what generates REM sleep?
generated by cells in the brainstem, particularly the pons, adjacent portions of the midbrain and hypothalamus
describe REM-on cells
are maximally active
in REM sleep.
Subgroups of REM-on cells use the transmitters GABA, glycine, acetylcholine or glutamate.
describe REM-off cells
are minimally active
in REM sleep.
Subgroups of REM-off cells use the transmitters norepinephrine, epinephrine, serotonin and histamine.
Cognitive deficit persists for ______days after the period of sleep deprivation (more deficits after lack of NREM than REM sleep)
several
do blind people suffer from sleep abnormalities?
yes
what are the various disorders of sleep?
-Insomnia
-Sleepiness during the Day
-Periods of Sleep Apnea cause frequent Awakenings
-Parasomnias
-Sleep Disorders involving Abnormal
Movement
-Disordered Sleep in Alzheimer’s and Parkinson’s Diseases
-Treating Sleep Disturbances
what known disorders are irregular sleeping behavior found in?
- Epilepsy
- Parkinson’s disease
- Alzheimer’s disease
- Prion diseases
- Schizophrenia
- Depression
- Stress
- Induced by alcohol and drugs
what are the two types of insomnia?
transient (less than 3 weeks)
chronic (elderly, pts with pain, psych pt, familial disorder)
*insomnia may also be due to drugs or alcohol abuse
what disorders of sleep fall under excessive sleepiness during the day?
Narcolepsy
- rapid onset of REM sleep
- cataplexy (sleep paralysis)
- hypnagogic hallucinations (pre-sleep dreams)
Sleepapnea
-interruptions in breathing (> 10 seconds) hypoxia & hypercapnia
Fatal familial insomnia
Prion disease (autosomal dominant disorder) selective atrophy of thalamic nuclei ANS: sympathetic overactivity
describe parasomnias
Parasomnias (mostly observed in children)
-Sleepwalking & Sleep Terrors (usually in
stages 3 & 4 NREM)
-Nightmares (during REM)
-Sleep paralysis (often in narcoleptic patients)
-Sleep myoclonus (jerks, startle) occurs during the initial phases of sleep, especially at the moment of dropping off to sleep
descibe Restless Legs syndrome
– Symptoms distantly resembling early Parkinson’s disease, but not caused by the same reasons
– Waking up after a short sleep, delays sleep onset
– During NREM periodic limb movements (PLMS) causing interruptions to sleep (benzodiazepines suppress arousals)
– Treated also by L-DOPA
– Keeping legs in cold, stretch, massage etc. may help
– Postulated problem: Iron metabolism (needed for an enzyme)
– NOT suffered only by elderly, occasionally
during pregnancy, can be of genetic origin
describe REM behavior disorder
- Failure of brainstem circuits to suppress muscular contraction during REM sleep
- Potentially harmful effects of violent limb movements during REM sleep correlated with content of dreams
what are tx options for sleep disorders?
- Behavioural therapy => change of sleep routines or daily activity patterns. SLEEP IS NECESSARY FOR MEMORY FORMATION!!!!
- Pharmacological => antidepressants, benzodiazepine and melatonin receptor agonists, dopamine agonists
- Caffeine inhibits A1 adenosine receptors. But be aware of developing tolerance!
neuronal activation in the HIPPOCAMPUS during REM sleep may play a role in?
memory
The hippocampo-cortical activation during waking is followed by multiple waves of cortical ____ during full sleep cycles
plasticity
• Early-life REM deprivation reduces______of hippocampal neuronal circuits, possibly by hindering expression of mature glutamatergic synaptic components
stability
the 4 stages of NREM sleep have progressive _____ levels of consciousness (sync, low freq. waves in EEG)
decreasing
periods of REM sleep have a ____ level of consciousness? (desync, high freq waves in EEG)
raised
the fraction of sleep time spent in NREM peaks at ____
puberty
the fraction of REM sleep time is ______ of age after puberty
independent
sleep deprivation is damaging to ____ and ____ ability
cognitive and manual
what is in the basal forebrain and brainstem that keeps us awake and alert?
the arousal system
all sleep disorders lead to subnormal ___ and ___ performance during waking hours
mental and physical
read about the documented abnormal people
- ♀ who sleeps for 1.5hours/night
- ♂ war veteran with shrapnel in his pons exhibits virtually no REM sleep
- ♂ observed in clinic experienced over 3hours of REM sleep
- ♂ stayed awake for 11 straight days without any Rx and had no permanent harmful effects
how can sleep deprivation help those who are clinically depressed
have unusually large amounts of REM sleep where controlled deprivation can help alleviate their
symptoms either with behavior changes or Rx
which is more significant in terms of the cognitive deficits seen: NREM deprivation or REM deprivation?
NREM
lesions of the brainstem can induce?
sleep/coma
how do general anesthetics lower consciousness?
by reducing the activity of the brainstem as part of the ARAS
what is the onset of REM due to?
firing of the pontine cholinergic cells (part of ARAS) which ↓firing rate in locus ceruleus and ↓raphe nucleus as well as an ↑LGN excitability and ↑Occipital Cortex V1 (dreams)
