sleep theories and physiology

8/10/2019 Sleep theories and physiology

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Biological Rhythms

a. types of biological rhythms

b. neurohormones

Sleepa. functions of sleepb. measuring sleep

c. dreamingd. neural mechanismse. sleep disorders


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Sigmund Freud (1900) In terpre ta tion of Dreams

water = birthflying = sexual arousalknifes, swords = castration anxietymud = fecescave, hallway = mother


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Freud Repressed memories and expression of libido.

Activation synthesis theory Sensory experiences are fabricated by the cortex as a means of interpreting

signals from the PGO activity.

Continual activation theory Encoding of short term procedural memories into long-term memories.

Dream theories


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Sleep is not a passive process

Cerveau isole

Mesencephalon transection Continuous sleep

Encephale isole

Brainstem transection Permanent insomnia


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Sleep/Waking Flip -Flop

vlPOA= ventrolateral preoptic areaACh = acetylcholineNE = norepinephrine

5-HT = serotonin


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Ventrolateral Preoptic Area

GABA neurons Activation promotes sleep. Destruction results in total insomnia.


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Locus Coeruleus

Norepinephrine neurons Located in the pons near the rostral end of the floor of the fourth ventricle. Involved in arousal and vigilance. Decreased activity during sleep (both slow-wave and REM)


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Locus coeruleus


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Acetylcholine Cholinergic neurons located in the pons and basal forebrain produce

activation and cortical desynchrony. Serotonin (5-HT)

Appears to play a role in activating behavior. Histamine

Neurotransmitter that increases wakefulness and arousal; found intuberomammillary nucleus of hypothalamus, just rostral to mammillarybodies.

Hypocretin (orexin) A peptide produced by neurons whose cell bodies are located in the

hypothalamus and project to arousal mechanisms; destruction causesnarcolepsy.


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Neural control of REM sleep PGO wave (pontine, geniculate, occipital):

Bursts of phasic electrical activity originating in the pons, followed by activity the lateral geniculate nucleus and visual cortex.

Peribrachial area The region in the pons; contains acetylcholinergic neurons involved in the

initiation of REM sleep.


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Sleep Disorders Insomnia

Affect approximately 25% of the population No single definition of insomnia

May be a symptom of physical ailment. Sleep apnea

Cessation of breathing while sleeping. Can be mediated centrally or locally (obstructive). May play a role in sudden infant death syndrome.

Narcolepsy

Disorder characterized by periods of irresistible sleep, attacks of cataplexy, sleeparalysis, and hypnagogic hallucinations. Treat with stimulant medications.


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Cataplexy

Paralysis during waking. Sleep paralysis

Paralysis just before a person falls asleep. Hypnagogic hallucination

Vivid dreams that occur just before a person falls asleep; accompanied by sleepparalysis.

Nocturnal enuresis Bedwetting

Somnambulism Sleepwalking

Pavor nocturnus Night terrors


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FDA-Approved Medications Benzodiazepines

estazolam (Prosom) flurazepam (Dalmane) quazepam (Doral) temazepam (Restoril) triazolam (Halcion)

Benzodiazepine Agonists eszopiclone (Lunesta) zaleplon (Sonata) zolpidem (Ambien)

Melatonin Agonists ramelteon (Rozerem)


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450 BC - Ancient Greek physician Alcmaeon ,sleep, describing it asloss of consciousness as blood retreats from the surface of the body

350 BC - Aristotle states sleep caused by warm vapours rising fromthe heart during digestion,concludes that sleep is a time of physicalrenewal

1862 - Italian scientist Sante de Sanctis concludes that animals drea just like people

1929 - Hans Berger develops an electroencephalograph device torecord brain waves, and notes differences in brain activity duringsleep and wakefulness


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SLEEP IS PASSIVE (HYPOTHESIS) BREMER 1929

Cerveau isole

Mesencephalon transection Continuous sleep

Encephale isole

Brainstem transection Permanent insomnia


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Sleep is active process Moruzzi AND Magoun (1949)that high-frequency stimulation of the midbrain reticular formation(the RAS) produces the EEG alerting response and arouses a sleepinganimal.Electrical stimulation of the posterior hypothalamus also produces

arousal similar to that elicited by stimulation of the midbrain, whileelectrical stimulation of the anterior hypothalamus and adjacent basalforebrain region induces sleep.


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RAS POLYSYNAPTIC PATHWAYProject diffusely from brain stem reticular formation to corteDirectly or via thalamus

Strong non specific RAS stimulationMainly responsible for awake state


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wakefulness Neural part RAS + sensory input to cortex -- Basal foreb

Non specifithalamic sySub thalam

Hypothalam

Visceral or somaticsensory input

Cortex


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Chemical part

LC LOCUS COERULUS ----NA

BF BASAL FOREBRAIN----ACHPH POSTERIOR HYPOTHALAMUS ---HIST.CORTEX ---- GLUTAMATEFROM BLOOD --- GLUCORTICOID

FROM CSF --- SUB.P

,HYPOTHALAMICRELEASING FACTOR, VIPADDITIONAL -IN IMAGE


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SLEEPSleep is defined as unconsciousness from which the person can bearoused by sensory or other stimuli

CONTROLLING FACTORS OF SLEEP FACTORS WHICH CONTROL CICARDIAN CYCLE

SUPRACHIMATIC NUCLEUS(BIOLOGICAL CLOCK)

REGULATE TIMING OF SLEEPONLY


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RECEPTOR

NA

MTRECEPTOR


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TYPE AND STAGES OF SLEEPWITH THE HELP OF POLYSOMNOGRAPY

NON RAPID EYE MOVEMENT SLEEP(NREM)/(SLOW WAVE SLEEP)4 STAGES BASED ON EEG (MAINLY)

RAPID EYE MOVEMENT SLEEP(REM)/(FAST WAVESLEEP)/(PARDOXICAL SLEEP)

Alpha awake rest with eye close SLEEP EE


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Alpha awake rest with eye close8 -13 Hz amp 50 uV

Beta arousal response

14 30 Hz amp 5 -10 uV

Theta wave not occur in normalwaking individual ( except new borns)4 7 Hz amp 10 uV

Delta wave deep sleepLess than 4 Hz amp 20-200 uVStrictly in cotex , release from controlof lower centres

SLEEP EE


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stage 1 st sleep cycle%1st NREM 5

2nd NREM 20

3rd NREM 30

4 th NREM 40

REM 5 EACH CYCLE APPROX 9 MIN


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NREM(SYNCHRONISED/SWS) NEURAL PART 1)Diencephalic sleep zone post. Hypothalamus --- waking centr

Ant. Hypothalamus --- sleep facilitatory c

2)Medullary sleep zone at level of tractus solitaris

3)Basal forebrain sleep zone preoptic area & diagonal band of b

8

Low Frquency sleep

High/lowfrequency

Contain GABA ergic inhibitory neurons (non REM on cell)


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Non REM on cell ------ GABA

Post. Hypothalamus(wake centre)-- HIS.

Nucleus reticularis

pontis oralis (PRO) ---ACH

Synchronised wave because of rhythmic projection of thalamic relay neurons in cortexThis rhythmicity due to GABA inhibitory neurons which form shell around thalamus


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REM(fast wave sleep/desynchronisesleep ) Neural part 1)Cholinergic neurons of brain and dorsal pons ---- ACH

GABA ergicneurons

RPOactivation


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2)Role of nucleus reticularis pontine oralis (RPO) PGO wave generation lat. Pontine tegmentum lat.GeniculatOccipital cortex

A)PGO on cell ---ach

C)REM waking on cell high rate firing during waking up & during

D)REM on cell high rate firing only during REMSome cell secrete GABA --- inhibit serotonin and NA. secreating cellSome cell secrete Glutamate ---- lower ms. tone

B) PGO off cellSerotonin raphe NA locus coeruluHist. post hypoth

PGO spike


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Chemical part-

Other endogenous sleep producingSub.1) Muramyl dipeptide

2) IL 13) Adenosin

Sleep Disorders


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Sleep Disorders

InsomniaAffect approximately 25% of the population

No single definition of insomniaMay be a symptom of physical ailment. Sleep apneaCessation of breathing while sleeping.Can be mediated centrally or locally (obstructive). Fatal familial insomniaWorsening insomnia , impaired ANS function ,dementia ,death NarcolepsyDisorder characterized by periods of irresistible sleep, attacks ofcataplexy, sleep paralysis, and hypnagogic hallucinations.


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Cataplexy

Paralysis during waking. Sleep paralysis

Paralysis just before a person falls asleep. Hypnagogic hallucination

Vivid dreams that occur just before a person falls asleep; accompanied by sleepparalysis.

Nocturnal enuresis Bedwetting

Somnambulism Sleepwalking

Pavor nocturnus Night terrors


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SleepSleep is defined as unconsciousness from which the person can bearoused by sensory or other stimuli


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Two Types of Sleep-Slow-Wave Sleep and Rapid Eye Movement (REM)

Sleep (1) slow-wave sleep, in which the brain waves are strong and of low

frequency, as we discuss later, and (2) rapid eye movement sleep (REMsleep),

Most sleep during each night is of the slow-wave variety; this is the deep

restful sleep that the person experiences during the first hour of sleep aftehaving been awake for many hours. REM sleep, on the other hand, occurin episodes that occupy about 25 percent of the sleep time in young adulteach episode normally recurs about every 90 minutes. This type of sleep not so restful, and it is usually associated with vivid dreaming.


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decreases in both peripheral vascular tone and many other vegetativ

functions of the body. For instance, there are 10 to 30 percentdecreases in blood pressure, respiratory rate, and basal metabolicrate.

REM Sleep (Paradoxical Sleep, Desynchronized Sleep) In a normanight of sleep, bouts of REM sleep lasting 5 to 30 minutes usuallyappear on the average every 90 minutes. When the person isextremely sleepy, each bout of REM sleep is short and may even beabsent. Conversely, as the person becomes more rested through thenight, the durations of the REM bouts increase.


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REM sleep has several important characteristics

dreaming and active bodily muscle movements more difficult to arouse by sensory stimuli than during deep slow-wave

sleep, and yet people usually awaken spontaneously in the morning durinan episode of REM sleep.

Muscle tone throughout the body is exceedingly depressed, indicatingstrong inhibition of the spinal muscle control areas. Heart rate and respiratory rate usually become irregular paradoxical sleep -brain is highly active metabolism may be increased

much as 20 percent(EEG) shows a pattern of brain waves similar to thosethat occur during wakefulness.


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Basic Theories of Sleep the reticular activating system, simply fatigued during the waki

and became inactive as a result. This was called the passive thsleep

An important experiment changed this view to the current belief thasleep is caused by an active inhibitory process: it was discovertransecting the brain stem at the level of the midpons creates a brainwhose cortex never goes to sleep. In other words, a center locatedbelow the midpontile level of the brain stem appears to be requiredto cause sleep by inhibiting other parts of the brain


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Possible raphe nuclei in the lower half of the pons and in the medulla

Nerve fibers from these nuclei spread locally in the brain stemreticular formation and also upward into the thalamus,hypothalamus, most areas of the limbic system, and even theneocortex of the cerebrum

fibers extend downward into the spinal cord, terminating in theposterior horns, where they can inhibit incoming sensory signals,including pain,


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drug that blocks the formation of serotonin is administered to ananimal, the animal often cannot sleep for the next several days.Therefore, it has been assumed that serotonin is a transmittersubstance associated with production of sleep.

Stimulation of some areas in the nucleus of the tractus solitariusalso cause sleep

Sleep can be promoted by stimulation of several regions in thediencephalon, including (1) the rostral part of the hypothalamus,mainly in the suprachiasmal area, and (2) an occasional area in thediffuse nuclei of the thalamus.


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Lesions in Sleep-Promoting Centers Can Cause Intense Wakefulnes Discrete lesions in the raphe nuclei lead to a high state of

wakefulness. This is also true of bilateral lesions in the mediasuprachiasmal area in the anterior hypothalamus. In both insthe excitatory reticular nuclei of the mesencephalon and upper ponsseem to become released from inhibition, thus causing the intense

wakefulness. Indeed, sometimes lesions of the anterior hypothalamcan cause such intense wakefulness that the animal actually dies ofexhaustion

Other Possible Transmitter Substances


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Other Possible Transmitter SubstancesRelated to Sleep Experiments have shown that the cerebrospinal fluid and the blood or

urine of animals that have been kept awake for several days contain asubstance or substances that will cause sleep when injected into the brainventricular system of another animal. One likely substance has beenidentified as muramyl peptide, a low-molecular-weight substance

only micrograms of this sleep-producing substance are injected into thethird ventricle, almost natural sleep occurs within a few minutes and theanimal may stay asleep for several hours. Another substance that hassimilar effects in causing sleep is a nonapeptide isolated from the blood osleeping animals. And still a third sleep factor, not yet identifiedmolecularly, has been isolated from the neuronal tissues of the brain stemof animals kept awake for days.

P ibl C f REM Sl


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Possible Cause of REM Sleep Why slow-wave sleep is broken periodically by REM sleep is not

understood. However, drugs that mimic the action of acetylcholineincrease the occurrence of REM sleep

postulated that the large acetylcholine-secreting neurons in the uppebrain stem reticular formation might, through their extensive efferenfibers, activate many portions of the brain.


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Cycle Between Sleep and Wakefulness sleep centers are not activated, the mesencephalic and upper pontile

reticular activating nuclei are released from inhibition, which allowthe reticular activating nuclei to become spontaneously active

This in turn excites both the cerebral cortex and the peripheralnervous system, both of which send numerous positive feedbacksignals back to the same reticular activating nuclei to activate themstill further. Therefore, once wakefulness begins, it has a naturaltendency to sustain itself because of all this positive feedback activ


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after the brain remains activated for many hours, even the neurons

themselves in the activating system presumably become fatigued.Consequently, the positive feedback cycle between themesencephalic reticular nuclei and the cerebral cortex fades and thesleep-promoting effects of the sleep centers take over, leading torapid transition from wakefulness back to sleep.

Physiologic Functions of Sleep Are Not


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y g pYet Known mild sleep restriction over a few days may degrade cognitive and

physical performance, overall productivity, and health of a person fact that rats deprived of sleep for 2 to 3 weeks may actually die Sleep causes two major types of physiologic effects: first, effects on

the nervous system itself, and second, effects on other functionalsystems of the body

nervous system effects seem to be by far the more important becausany person who has a transected spinal cord in the neck (andtherefore has no sleep-wakefulness cycle below the transection)shows no harmful effects in the body beneath the level of transectiothat can be attributed directly to a sleep-wakefulness cycle.


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that sleep in multiple ways restores both normal levels of brain

activity and normal "balance" among the different functions of thecentral nervous system. This might be likened to the "rezeroing" ofelectronic analog computers after prolonged use because computersof this type gradually lose their "baseline" of operation; it isreasonable to assume that the same effect occurs in the centralnervous system because overuse of some brain areas duringwakefulness could easily throw these areas out of balance with theremainder of the nervous system.


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Sleep has been postulated to serve many functions including (1)

neural maturation, (2) facilitation of learning or memory, (3)cognition, and (4) conservation of metabolic energy.

The specific physiologic functions of sleep, however, remain amystery, and they are the subject of much research.


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Brain Waves Electrical recordings from the surface of the brain or even from the

outer surface of the head

The intensities of brain waves recorded from the surface of the scalrange from 0 to 200 microvolts, and their frequencies range fromonce every few seconds to 50 or more per second.


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The character of the waves is dependent on the degree of activity in

respective parts of the cerebral cortex, and the waves changemarkedly between the states of wakefulness and sleep and coma.

Alpha waves are rhythmical waves that occur at frequencies betwee8 and 13 cycles per second and are found in the EEGs of almost allnormal adults when they are awake and in a quiet, resting state ofcerebration. These waves occur most intensely in the occipital regiobut can also be recorded from the parietal and frontal regions of thescalp. Their voltage is usually about 50 microvolts. During deep slethe alpha waves disappear


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When the awake person's attention is directed to some specific type

of mental activity, the alpha waves are replaced by asynchronous,higher-frequency but lower-voltage beta waves. Figure 59-2 the effect on the alpha waves of simply opening the eyes in brightlight and then closing the eyes. Note that the visual sensations causimmediate cessation of the alpha waves and that these are replacedby low-voltage, asynchronous beta waves.


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Beta waves occur at frequencies greater than 14 cycles per second

and as high as 80 cycles per second. They are recorded mainly fromthe parietal and frontal regions during specific activation of theseparts of the brain.

Theta waves have frequencies between four and seven cycles persecond. They occur normally in the parietal and temporal regions in

children, but they also occur during emotional stress in some adultsparticularly during disappointment and frustration. Theta waves alsoccur in many brain disorders, often in degenerative brain states.


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Delta waves include all the waves of the EEG with frequencies les

than 3.5 cycles per second, and they often have voltages two to fourtimes greater than most other types of brain waves. They occur invery deep sleep, in infancy, and in serious organic brain disease

intensity of the brain waves from the scalp is determined mainly by

the numbers of neurons and fibers that fire in synchrony with oneanother, not by the total level of electrical activity in the brain. In fastrong nonsynchronous nerve signals often nullify one another


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when the eyes were closed, synchronous discharge of many neuron

in the cerebral cortex at a frequency of about 12 per second, thuscausing alpha waves. Then, when the eyes were opened, the activityof the brain increased greatly, but synchronization of the signalsbecame so little that the brain waves mainly nullified one another.The resultant effect was low voltage waves of generally high butirregular frequency, the beta waves.


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Origin of Alpha Waves Alpha waves will not occur in the cereb

cortex without cortical connections with the thalamus. Conversely,stimulation in the nonspecific layer of reticular nuclei that surthe thalamus or in "diffuse" nuclei deep inside the thalamus oftensets up electrical waves in the thalamocortical system at a frequencybetween 8 and 13 per second, which is the natural frequency of thealpha waves. Therefore, it is believed that the alpha waves result frospontaneous feedback oscillation in this diffuse thalamocorticalsystem, possibly including the reticular activating system in the brastem as well. This oscillation presumably causes both the periodicitof the alpha waves and the synchronous activation of literally millioof cortical neurons during each wave.


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Origin of Delta Waves Transection of the fiber tracts from the

thalamus to the cerebral cortex, which blocks thalamic activation ofthe cortex and thereby eliminates the alpha waves, nevertheless doenot block delta waves in the cortex. This indicates that somesynchronizing mechanism can occur in the cortical neuronal systemby itself-mainly independent of lower structures in the brain-to causthe delta waves

Delta waves also occur during deep slow-wave sleep; this suggeststhat the cortex then is mainly released from the activating influenceof the thalamus and other lower centers.


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There is a general correlation between level of cerebral activity and

average frequency of the EEG rhythm, the average frequencyincreasing progressively with higher degrees of activity. This isdemonstrated in Figure 59-3, which shows the existence of deltawaves in stupor, surgical anesthesia, and deep sleep; theta waves inpsychomotor states and in infants; alpha waves during relaxed stateand beta waves during periods of intense mental activity. Duringperiods of mental activity, the waves usually become asynchronousrather than synchronous, so the voltage falls considerably despitemarkedly increased cortical activity


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THALAMIC NUCLEI


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THALAMIC NUCLEI Th e nuclei that project to wide regions of the neo-cortex are the

midline and intralaminar nuclei. specifi c sensory relay nuclei and the nuclei concerned with efferen

control mechanisms. specifi c sensory relay nuclei include the medial and lateral

geniculate bodies, which relay auditory and visual impulses to the

auditory and visual cortices; and the ventral posterior lateral (VPL)and ventral posteromedial nuclei, which relay somatosensoryinformation to the postcentral gyrus


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RETICULAR ACTIVATING SYSTEM The reticular formation, the phylogenetically old reticular core of the brain, occupies the central portion of the medulla and midbrain, surrounding the fourth ventricle and cerebral aqueduct. The reticular formation contains the cell bodies and

fi bers of many of the serotonergic, noradrenergic, and cholinergic systems. Th ese pathways were shown in Figure 7 2 .


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reticular formation also contains many of the areas concerned with regulation of heart rate, blood pressure, and respiration.


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The reticular formation plays an important role in determining The

Level Of arousal, Thus It is called the ascending reticular ActivatinSystem (RAS)


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Th e EEG recorded from the scalp is a measure of the summation of dendritic postsynaptic potentials rather than action potentials ( Figure 14 4 ). Th e dendrites of the cortical neurons are a forest of similarly oriented, densely packed units in the superfi cial layers of the cerebral cortex ( Figure 14 1 ). Propagated potentials can be generated in dendrites. In addition, recurrent axon collaterals end on dendrites in the superfi - cial layers. As excitatory and inhibitory endings on the dendrites of each cell become active, current fl ows into and out of these current sinks and sources from the rest of the dendritic processes and the cell body. Th e cell body dendrite relationship is therefore that of a constantly shift ing dipole.


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sleep theories and physiology

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