Physiology of Sleep

A small go through the stages and physiologyof sleep.

1. SLEEP
KIRSHA K S
ASSISTANT PROFESSOR
DEPT. OF PHARMACY PRACTICE
KMCH COLLEGE OF PHARMACY
COIMBATORE-8

2. SLEEP
•Aphysicalandmentalrestingstateinwhich
apersonbecomesrelativelyinactiveand
unawareoftheenvironment.
•Sleepisapartialdetachmentfromtheworld,
wheremostexternalstimuliareblockedfrom
thesenses.

3. •So,sleepisnaturallyrecurringstateofmindand
body,characterizedbyalteredconsciousness,
relativelyinhibitedsensoryactivity,reduced
muscleactivityandinhibitionofnearly
allvoluntarymusclesduringrapideyemovement
(REM)sleep,andreducedinteractionswith
surrounding.
•Quality sleep –and getting enough of it at the
right times --is as essential to survival as food
and water

4. •Therearefourstagesofsleep:
Non-REM(NREM)sleep(Stages1,2,3
&4)
REMsleep.
•Periodsofwakefulnessoccurbeforeand
intermittentlythroughoutthevarioussleep
stagesorasoneshiftssleepingposition.

7. NREM
Stage1
•ThelighteststageofNREMsleep.
•Definedbythepresenceofsloweye
movements,thisdrowsysleepstagecanbe
easilydisruptedcausingawakeningsor
arousals.
•Muscletonethroughoutthebodyrelaxesand
brainwaveactivitybeginstoslowfromthatof
wake.
•Peoplemayexperiencehypnicjerksorabrupt
musclespasmsandmayevenexperience
sensationoffallingwhiledriftinginandoutof
stage1.
5%
5%

8. Stage2
•ThefirstactualstageofdefinedNREMsleep.
•AwakeningsorarousalsdonotoccuraseasilyasinStage1
sleepandtheslowmovingeyerollsdiscontinue.
•Brainwavescontinuetoslowwithspecificburstsofrapid
activityknownassleepspindlesintermixedwithsleep
structuresknownasKcomplexes.
•BothsleepspindlesandKcomplexesarethoughttoserveas
protectionforthebrainfromawakeningfromsleep.
•Bodytemperaturebeginstodecreaseandheartratebegins
toslow.
50%

9. Stage3and4DeltaSleep
•KnownasdeepNREMsleep.
•Thesearedeepsleepstages,withstage4beingmoreintense
thanstage3.Thesestagesareknownasslow-wave,ordelta,
sleep.
•Themostrestorativestageofsleep,stage3consistsofdelta
wavesorslowwaves.Alsobrainproducesextremelyslow
waveswithoccasionalburstsoffasterbrainwaveactivity
•Awakeningsorarousalsarerareandoftenitisdifficultto
awakensomeoneinStage3sleep.
•Parasomnias (sleepwalking, sleep talking
orsomniloquyandnightterrors)occurduringthedeepest
stageofsleep.
10-20%

10. •Stage4,ourbrainsproduceextremelyslowwavesalmost
exclusively.Thesestagesareknownas“DeepSleep”or
“DeltaSleep”.
•It'smostdifficulttowakeupduringthisstage.
•Duringthesestagesourbodiesemitgrowthhormonesand
workonrepairingphysicaldamagedoneduringtheday

11. REM
•Knownasrapideyemovement,ismostcommonlyknown
asthedreamingstage.
•Firstoccursabout90minutesafterfallingasleep.
•Eyemovementsarerapid,movingfromsidetosideand
brainwavesaremoreactivethaninStages2&3ofsleep.
•AwakeningsandarousalscanoccurmoreeasilyinREM;
beingwokenduringaREMperiodcanleaveonefeeling
groggyoroverlysleepy.
•EachREMstagecanlastuptoanhour.Anaverageadult
hasfivetosixREMcycleseachnight.Duringthisfinal
phaseofsleep,yourbrainbecomesmoreactive.
20%

12. •TheperiodofREMsleepismarkedbyextensive
physiologicalchanges.Theseinclude:
Acceleratedrespiration
Increasedbrainactivity
Eyemovement
Musclerelaxation
•ThefirstperiodofREMtypicallylasts10
minutes,witheachrecurringREMstage
lengthening,andthefinalonelastinganhour.

14. SLEEP CYCLE

15. •Asleepcycleistheprogressionthroughthe
variousstagesofNREMsleeptoREMsleep
beforebeginningtheprogressionagainwith
NREMsleep.
•Thesleepcycleisanoscillationbetween
theslow-waveandREM(paradoxical)phases
ofsleep.
•Itissometimescalledtheultradiansleep
cycle,sleep–dreamcycle,orREM-NREM
cycle.

16. •Apersonwouldbeginasleepcycleevery90-
120minutesresultinginfourtofivecyclesper
sleeptime,orhoursspentasleep.
•Asleepcycleprogressthroughthestagesof
non-REMsleepfromlighttodeepsleep,then
reversebackfromdeepsleeptolightsleep,
endingwithtimeinREMsleepbeforestarting
overinlightsleepagain.

18. Thefirstsleepcycletakesabout90minutes.
Afterthat,averagebetween100to120
minutes.
Typically,anindividualwillgothroughfourto
fivesleepcyclesanight.

21. NNNN
BB
NREM
1
NREM
2
NREM 3
NREM
4
NREM
3
NREM
2
REM
BRIEF
AWAKENING

22. SLEEP-WAKE
REGULATION
THE
TWO-
PROCESS
MODEL
PROCESS
C
PROCESS
S
Maintains
wakefulness
Promotes
sleep

23. Electrophysiological changes
during sleep

24. •ProcessSisthehomeostatic
driveforsleep.
•Theneedforsleep(process
S)accumulatesacrossthe
day,peaksjustbefore
bedtimeatnightand
dissipatesthroughoutthe
night.
•ProcessCiswake
promotingandisregulated
bythecircadiansystem.
•ProcessCbuildsacrossthe
day,servingtocounteract
processSandpromote
wakefulnessandalertness.
Thiswake-promotingsystembeginstodeclineatbedtime,servingtoenhance
sleepconsolidationastheneedforsleepdissipatesacrossthenight.Withan
adequatenight’srest,thehomeostaticdriveforsleepisreduced,thecircadian
wakingdrivebeginstoincrease,andthecyclestartsover.ProcessCalso
workstoconsolidatesleepandwakeintofairlydistinctepisodes.Through
synchronizationofthecircadiansystem,processCassistsinkeepingsleep-
wakefulnesscyclescoordinatedwithenvironmentallight-darkcycles.

25. Sleep-Generating Systems in
the Brainstem
•SleepprocessSisregulatedby
neuronsthatshutdownthearousal
systems,thusallowingthebraintofall
asleep.
•Theseneuronsarefoundinthepreoptic
areaofthehypothalamus.These
neurons,containingmoleculesthat
inhibitneuronalcommunication,
turnoffthearousalsystemsduring
sleep.
•Initiationandmaintenanceofsleep
requiresuppressionofactivityinthe
ascendingarousalsystems.Thisis
accomplishedbyinhibitoryneuronsof
theventrolateralpreopticarea(VLPO)
whichremainactivethroughoutsleep

26. •Themolecular“triggers”thatactivate
theVLPOandinitiatesleep,pointsto
extracellularadenosineasa
candidate.
•Adenosineaccumulatesinbasal
forebrainduringwakefulnessand
diminisheswithongoingsleep.
•Adenosinereceptorsareexpressedin
theVLPOandadenosineactivates
VLPOneuronsinvivo,makingita
reasonablecandidateforthe“sleep
switch.”
Othermoleculesalsoplayimportantsignalingrolescontrollingtheinitiationand
maintenanceofsleep.ThemonoaminergicarousalcentersprojecttotheVLPOand
mayservetoinhibititsactivity.Thiscreatestheconceptof“flip-flop”controlof
behavioralstate,inwhich,atanygiventime,activityofeitherarousalproducingor
sleep-producingneuronsdominatesandsuppressestheother.
Inaddition,theVLPOreceivesimportantcircadianmodulationfromthe
suprachiasmaticnucleus—thecentralcircadianclock.

27. Wake-Generating Systems in
the Brainstem
Wakefulnessisgeneratedbyanascendingarousal
systemfromthebrainstemthatactivatesforebrain
structurestomaintainwakefulness.
Thecorticalactivationnecessarytomaintain
wakefulnessissupportedbyanextensivenetworkof
subcorticalstructuresandpathways.
Majorneurochemicalsofthis“ascendingarousal
system”include:
•Excitatorynorepinephrinearisingfromthelocus
ceruleus(LC)
•Serotoninfromthemidlineraphenuclei
•Histaminefromthetuberomammillarynucleus
•Dopaminefromtheventralperiacqueductalgray
matter
•Acetylcholinefromthepedunculopontine
tegmentum,andthelaterodorsaltegmentumofthe
pons
•Orexinfromtheperifornicalarea.

28. Themainsourcefortheascendingarousalinfluenceincludestwo
majorpathwaysthatoriginateintheupperbrainstem.
Ultimately,alloftheseinputsenterthecerebralcortex,wheretheydiffuselyactivate
thenervecellsandpreparethemfortheinterpretationandanalysisofincoming
sensoryinformation.
Thesecondpathway,whichoriginatesincell
groupsintheupperbrainstemthatcontainthe
monoamineneurotransmittersentersthe
hypothalamus,ratherthanthethalamus,where
itpicksupinputsfromnervecellsthatcontain
peptides(orexinorhypocretinandmelanin-
concentratinghormone).
Thefirstpathway,whichtakesoriginfromcholinergicneuronsin
theupperpons,activatespartsofthethalamusthatareresponsible
formaintainingtransmissionofsensoryinformationtothecerebral
cortex.
Theseinputsthentraversethebasal
forebrain,wheretheypickupadditional
inputsfromcellscontainingacetylcholine
andgamma-aminobutyricacid.

29. THE 24-HOUR CLOCK
CIRCADIAN
RHYTHMS
Regulate body
temperature,
heart rate
Modulate
physical
activity and
food
consumption
Regulate
muscle tone,
and hormone
secretion
Control the
sleep-wake
cycle
Circadian
rhythms refer,
collectively, to
the daily
rhythms in
physiology and
behavior.

30. ThemaininfluenceoftheSCNon
sleepisduetoaseriesofrelays
throughthedorsomedialnucleus
ofthehypothalamus,which
signalstothewake-sleepsystems
tocoordinatetheiractivitywith
theday-nightcycles.

31. •Therhythmsaregeneratedbyneuralstructuresinthe
hypothalamusthatfunctionasabiologicalclock.
•Thebasisfortheseclocksisbelievedtobeaseriesof
molecularpathwaysinvolving“clock”genesthatare
expressedinanearly24-hourrhythm.
•Thesuprachiasmaticnucleus(SCN)isresponsiblefor
regulatingcircadianrhythmsinallorgans.
•Itreceivesdirectinputsfromaclassofnervecellsinthe
retinathatactasbrightnessdetectors,whichcanresetthe
clockgenesintheSCNonadailybasis.
•TheSCNthentransmitstotherestofthebrainandbody
signalsthatbringallofthedailycyclesinsynchronywith
theexternaldaynightcycle.

33. SUMMARY
•Sleepitselfisnotahomogenousprocess.
•Thereexisttwofundamentallydistincttypesof
sleep:rapideyemovement(REM)sleep,
whichisassociatedwithactivedreaming,and
non–rapideyemovement(NREM)sleep.
•Sleepcycle
•ProcessCandProcessS
•CircadianRhythm

34. REFERENCE
1.MichaelSchupp,ChristopherDHanning.Physiologyofsleep.
BritishJournalofAnaesthesia2003;3(3):69-74
2.SleepPhysiology-SleepDisordersandSleepDeprivation.
https://www.ncbi.nlm.nih.gov/books/NBK19956/
3.DavidWC,SarahFS.PhysiologyofSleep.AmericanDiabetes
Association.DOI:10.2337/diaspect.29.1.5
4.https://www.ninds.nih.gov/Disorders/Patient-Caregiver-
Education/Understanding-Sleep
5.https://www.tuck.com/stages/#stages_of_the_sleep_cycle
6.https://www.sleepfoundation.org/articles/teens-and-sleep
7.https://www.deltasleeper.com/stagesofsleep/
8.https://www.sleep.org/articles/what-happens-during-sleep/
9.https://my.clevelandclinic.org/health/articles/12148-sleep-basics