Sleep 1

DRUGS
“sleep latency”= time from which ur awake till asleep

benzodiazepine= suppresses SWS, ^GABA , poor quality of sleep

antidepressants/ SSRI= suppress REM, increase sleep
opiates= reduce REM
lithium, anti-psychotics= increase SWS
alcohol= reduce sleep latency, increase SWS, suppress REM-cause fragmented sleep
b-blockers + thyroid medications= insomnia, increase sleep latency
caffeine+nicotine= increase sleep latency, reduce SWS

 sleep seems to be inversely proportional to animal size.

 sleep= state of reduced consciousness with reduced responsiveness to env
and internal stimuli
 anabolic state: restores immunity, reduces imflammation, replenishes ATP,
signals endocrine system to modulate certain hormones.
 REM/dream sleep= memory consolidation and learning
 no sex differences in sleep
 sleep requirements change with age
 sleep is essential for cognition: even mild sleep deprivation causes
performance changes
 error rate increases for each hour less of sleep
 Wakefullness
 1- brainstem ascending reticular arousal system formation: send to
thalamus, then to cortex for stimulation of wakefulness = glutamate
 locus cereleus = NE from brainstem to cortex
 2- posterior hypothalamus = histamine + orexin
 3- basal forebrain= acetylcholine
 awake: EEG= 8-12 spikes per second: alpha waves
 go from bottom up = brainstem-cortex
 Sleep
 shift from sympathetic to parasympathetic
 activating systems (^) are dampened
 anterior hypothalamus: GABA neurons
 inhibition of activating systems of wakefulness= GABA neurons in anterior
hypothalamus
 note: serotonergic raphe neurons- sleepy in some wakefulness in others
 sleep is maintained by the constant inhibitory effect on the cortex
mediated via the thalamus
 EEG: SLOW frequency, high voltage brain activity
 gaba released by melatonin
 complex multifactorial event depending on environment, neuro-behavioral,
physiological

 Circadian rhythm
 resides in the supra chiasmatic nucleus in the anterior hypothalamus
 SCN controls the timing of circadian rhythms in mammals
 human rhythm = 24.2h
 supra chiasmatic nucleus
 genetically encoded function with clock genes, time and period genes ,
feedback loop and support an endogenous self contained rhythm
 the duration of this rhythm= circadian rhythm
 produce one product and degrade It in a loop time of 24h
 these genes get activated every 24.2 h
 SCN  controls secretion of pineal output of melatonin (melatonin
production is inhibited by light
 retinohypothalamic tract
 the SCN receives direct retinal input from retina via a monosynaptic
pathway
 info about light from the env reaches SCN
 SCN controls secretion of pineal output of melatonin (melatonin production
is inhibited by light
 one of the longest monosynaptic pathways
 overall: retina-- (one axon) --SCN : + pineal gland melatonin (reaches
anterior hypothalamus)  +GABA production --- > sleep 
 Activated: no light
 inhibited: light
 sunlight: shutdown of melatonin = decreased GABA= system starts working,
you wake up
 this is disturbed by phone=light
 broadband white light suppresses melatonin secretion from pineal gland
 optimal suppression of plasma melatonin= blue light (emitted by phones!)
 Melatonin secretion
 starts at 9pm
 peaks at 3am
 undetectable by 11am
 cant change LENGTH of circadian rhythm, but can shift it back or forth
depending on behavior (time where it starts/ends- but still has to be 24h)
 ex- in blind people, meal times will determine this

 Physiological Changes in Sleep

 non-REM sleep= parasympathetic. decreased skeletal and smooth muscle
tone in REM
 REM sleep= sympathetic, like being awake and agitated. reversible
paralysis, except ocular muscles and smooth muscles.
 CV: decreased HR and BP in non REM
 CV: variable in REM

 Endocrine Changes in sleep
 Leptin= secreted in the 1st part of the night= suppresses apetite
 ghrelin= secreted when youre sleep deprived= makes u eat
 cortisol= secreted in the AM
 testosterone= higher in the morning
 immune system = modulated by sleep
 growth hormone and prolactin= increased during sleep
 sleep deprivation= involved in weight gain and growth problems + pro-
inflamm cytokines and reduced immunity
 Physiologic Changes
 Respiratory
 nonREM: slow, rhythmic breathing
 REM: shallow erratic breathing, diaphragmatic breathing only (intercostal
and accessory resp muscles are paralyzed). many pts wake up with apnea
like events from REM
 GI and GU
 slower peristalsis and reduced gastric emptying and reduced bladder
contractility
 Age related sleep changes
 newborns= sleep almost 16h
 sleep requirements decrease with age
 stabilize in adulthood at 7.5h
 overall sleep is stable in adulthood and decrease in advanced age
 Sleep and the life cycle
 With age
 slow wave sleep= decreases
 stage 1= stable
 stage 2= increases
 REM= tends to remain stable
 sleep becomes lighter, more fragmented and we can be aroused asier as
we age
 first part of the night: slow wave sleep (SWS) = needed to physically
replenish
 second part of the night: REM sleep (more dreaming)
 Sleep Stages
 start= non REM: stages 1, 2, and SWS
 then= non REM+ REM
 REM sleep= 4-6 episodes throughout
 alternate every 90min btw: non REM (stages 1-4) and REM
 Slow wave sleep= 1st third of nocturnal sleep
 REM predominates the last third of nocturnal sleep (early morning)
 -stage 2= K complexes and sleep spindles
 K = largest physiological changes in brain and large in voltage
 -stage 3 and 4= large sinusoidal waves
 most difficult awakening in SWS
 SLEEP STAGES
 STAGE 1
 emg tone decrease
 attenuation of alpha rhythm (wake)
 low voltage
 theta rhythm 5-7hz (drowsiness)
 slow rolling eye movements
 vertex waves
 can easily be woken up while youre falling asleep, transient
 transition from wake to sleep
 STAGE 2
 K complexes= prevent you from waking up – biphasic sharp deflections
 sleep spindles= fast bursts on EEG
 STAGE 3 and 4/ SLOW WAVE SLEEP (SWS)
 deep sleep
 delta waves
 no eye movements
 reduced responsiveness= hardest to wake people in SWS
 (babies and children mostly SWS, reduced with age)
 similar delta waves found in someone under general anesthesia
 REM
 dreaming stage
 rapid sharp out of phase eye movements, looking quickly from side to side
 saw tooth waves on EEG
 EEG can resemble wakefulness
 EMG shows atonia= skeletal muscle paralysis
 increased HR and breathing less regular

 Dreaming
 not completely understood
 likely for learning and memory consolidation
 dreaming can happen in all stages, but in REM it is most vivid with content
 dreaming in other stages is usually mundane with no emotional content
 learning some behaviors?

note= increased dreaming+REM= biological marker for depression.

depressed people dream earlier in the cycle
antidepressants given = serotonin= dreaming stops
when pt stops the drug= rebound nightmares

 Drug Effects on Sleep

 benzodiazepine (Xanax) = increase GABA , poor quality of sleep. suppress
SWS
 antidepressants= suppress REM, but make u sleep more
 lithium + anti psychotics= increase SWS
 opiates= reduce REM
 beta blockers and thyroid medications= insomnia
 caffeine and nicotine= increased sleep latency and reduced SWS
 alchohol= makes you sleep = fragmentation sleep due to alcohol withdrawl,
short ½ life.
 thyroid medications= tell pt to take in AM