The Neural Mechanism of Sleep.

1. ISABELLA THOBURN COLLEGE
Neural Mechanism Of Sleep
SUBMITTED TO :
DEPARTMENT OF ZOOLOGY
SUBMITTED BY:
MADEEHA ZAIDI
M.Sc. Sem -2

2. WHAT IS SLEEP?
 Sleep Is A Physiological Process By Which
Bodily Functions Are Periodically Rested. During
Sleep, Consciousness And Power Of Will Are
Partially Or Completely Suspended And Bodily
Activity Generally Is Greatly Reduced.

3. 1- Slow-wave sleep (Non REM)- Non rapid eye
movement completes in 4 stages:
N1- Stage between sleep and wakefulness , it is lightest sleep.
Brain produces theta waves.
We experience Hypnogogic hallucination.
N2- Slightly deeper stage of sleep.
People in N2 are harder to awaken . We see more theta
waves.
N3 and N4- Also known as slow-wave sleep because brain waves are very slow.
These are called delta waves.
In this stage you are very much dead to the world.

4. SLEEP CENTERS
 Areas causing sleep when stimulated:
 1. Raphe nuclei in lower pons and medulla – Targets (efferents ):
Reticular formation, thalamus, neocortex, hypothalamus, limbic
system, dorsal roots of spinal cord – Neurotransmitter: Serotonin
(5HT). 2. *“Medullary
synchronization area” in nuc . Tractus solitaries level: • May
stimulate the Raphe nuclei?
 3. *Diencephalic sleep areas: 1. Rostral of hypothalamus,
especially the suprachiasmatic area 2. Intralaminar and anterior
thalamic nuclei
 4. Basal forebrain sleep area: 1. Preoptic area and Broca’s
diagonal band. *low frequency stimulation (8/s) leads to sleep;
while high freq. causes to wake up Sleep

5. Mechanisms controlling
sleep and wakefulness.
 What makes us sleep at night and wake
up each morning? To understand the
importance of sleep, it is helpful to know
something about the basic mechanisms
of the sleep-wake cycle. This cycle, which
consists of roughly 8 hours of nocturnal
sleep and 16 hours of daytime
wakefulness in humans, is controlled by a
combination of two internal influences:
sleep homeostasis and circadian rhythms.

6. Homeostasis
 It is the process by which the body maintains a “steady
state” of internal conditions such as blood pressure, body
temperature, and acid-base balance.
 The amount of sleep each night is also under homeostatic
control.
 From the time that we wake up, the homeostatic drive for
sleep accumulates, reaching its maximum in the late
evening when most individuals fall asleep.
 There is an evidence to indicate that one may be the
inducing chemical, adenosine (Neurotransmitter).

7. As long as we are awake, blood levels of adenosine rise continuously,
resulting in a growing need for sleep that becomes more and more difficult
to resist and vice-versa.
Certain drugs, like caffeine, work by blocking the adenosine receptor,
disrupting this process.

8. Circadian rhythms
 It refer to the cyclical changes—like fluctuations in body
temperature, hormone levels, and sleep—that occur over
24hour period, driven by the brain’s biological “clock.”
 In humans, the biological clock consists of a group of
neurons in the hypothalamus of the brain called the
Suprachiasmatic nucleus (SCN).
 These internal 24 hour rhythms in physiology and
behaviour are synchronized to the external physical
environment and social/work schedules. In humans, light
the strongest synchronizing agent.

9.  Light and darkness are external signals that “set” the biological clock and help
determine when we feel the need to wake up or go to sleep.
 In addition to providing synchronization in time between various rhythms, the
circadian clock also helps promote wakefulness.

10. Disruptions of the
Circadian System
 Conditions associated with a disruption of circadian rhythms include
shift work, jet lag and other circadian rhythm sleep disorders.
 In jet lag, times for sleep and wakefulness dictated by the internal
circadian clock do not correspond with external cues in the new time
zone.
 The result is excessive sleepiness, poor sleep, loss of concentration,
poor motor control, slowed reflexes, nausea, and irritability.
 Those who perform shift work, particularly on night shifts, also may
experience the effects of a disrupted circadian sleep-wake cycle; research
shows that 10 to 20 percent of shift workers report falling asleep on the
job.

11. A Physiological and
Behavioral Description
PHYSIOLOGICAL MEASURES
 Electroencephalogram (EEG)
 brain waves from scalp surface.

12.  Electromyogram (EMG):
An electrical potential recorded from
an electrode placed on a muscle.

13.  Electro-oculogram (EOG):
 An electrical potential from the
eyes, recorded by means of
electrodes placed on the skin
around them, detects eye
movements.

14.  Alpha activity:
 A smooth electrical activity of 8 –
12 Hz recorded from the brain;
generally associated with a state
of relaxation.
 Beta activity:
 Irregular electrical activity of 13 –
30 Hz recorded from the brain;
generally associated with a state
of arousal.
Sleep Stages

15. Theta activity:
EEG activity of 3.5 – 7.5 Hz that
occurs intermittently during early
stages of slow wave sleep and REM
sleep.
Delta activity:
Regular, synchronous electrical
activity of less than 4 Hz recorded
from the brain; occurs during the
deepest stages of slow-wave sleep.

16. 2-The last stage we need to know about is
REM Sleep.
 REM Sleep ( Rapid – Eye Movement )
 In this stage your eyes move really rapidly beneath your lids .
 Most of your muscles are paralysed.
 It is known as Paradoxical Sleep as your brain seems very
active and awake but your body is prevented from doing
anything.
In a normal night of uninterrupted sleep you cycle
through these stages about 4-5 times each. It takes about
90 mins to complete a cycle. The order within a cycle tends
to go from N1 N2 N3-N4 and then back to N2
before entering REM Sleep and then back to N1 and then it
starts all over again.

17. The major players in sleep were broken into
two categories:
 Sleep-agonists and Sleep-antagonists.
 The sleep-agonist areas are the median pre-optic nucleus, the ventrolateral
pre-optic nucleus, and the Pineal Gland .
 The sleep-antagonist areas are the raphe nucleus, the locus coeruleus, the
perifornical lateral hypothalamus, and the tuberomammillary nucleus.

18. Neurotransmitters and
centres for sleep regulation.
 Acetylcholine:
 One of the most important neurotransmitters involved in arousal.
 Two groups of acetyl cholinergic neurons located in the pons and basal forebrain, produce activation and cortical
desynchrony when they are stimulated.
 Norepinephrine:
 Catecholamine agonists produce arousal and sleeplessness; effects appear to be mediated by the locus coeruleus in the
dorsal pons.
 Locus ceoruleus:
 A dark-colored group of noradrenergic cell bodies located in the pons near the rostral end of the floor of the fourth ventricle;
in arousal and vigilance.

19.  Hypocretin:
 A peptide also known as orexin, produced by neurons whose cell bodies are located in
the hypothalamus; their destruction causes narcolepsy.
 Ventrolateral preoptic area (VLPA):
 A group of GABAergic neurons in the preoptic area whose activity suppresses alertness
and behavioral arousal and promotes sleep.
 Destruction of this area has been reporter to result in total insomnia, coma, and
death in rats

20.  Serotonin (5-HT):
 Appears to play a role in activating behavior; almost all of the brain’s serotonergic neurons are found in the
raphe nucleus, located in the medullary and pontine regions of the brain.
 Raphe nucleus:
 A group of nuclei located in the reticular formation of the medulla, pons, and midbrain, situated along the
midline; contain serotonergic neurons.
 Histamine:
 A neurotransmitter implicated in control of wakefulness and arousal; a compound synthesized
from histidine, an amino acid.
 Tuberomammillary nucleus:
 A nucleus in the ventral posterior hypothalamus, just rostral to the mammillary bodies; contains
histaminergic neurons involved in cortical activation and behavioral arousal.

21. Neural Mechanism Of Sleep.
Basal Forebrain
Brain Stem Reticular Formation
Raphe nucleus (midbrain)
Locus Coeruleus (pons)
Lateral hypothalamus

22.  Sleep is an active state
mediated by at least three
neural systems-
 Forebrain: generates SWS(slow-
wave sleep)
 Reticular Formation: Wakes
Forebrain
 Pons: Triggers REM sleep

23. BASAL FOREBRAIN
 ventral frontal lobe, anterior hypothalamus
 lesions abolish SWS( slow –wave sleep)
 electrical or heat stimulation can induce SWS activity
 These neurons are active at sleep onset
 Inhibited by NE stimulation

24. RETICULAR FORMATION
 Central stimulation produces arousal, awakens a sleeping animal
 lesions produce persistent sleep
 core of brain stem
 diffuse group of cells extending from medulla to thalamus
 electrical

25. RAPHE NUCLEI
 A system of serotonergic neurons along midline of brain stem.
 Lesions to Raphe nuclei produce insomnia.
 PCPA inhibits 5-HT synthesis and reduces sleep, whereas 5-HT
agonists promote sleep

26. PONS
 crucial for REM sleep components
 lesions ventral to Locus Coeruleus abolish REM sleep
 electrical or pharmacological stimulation (ACh agonists) can induce or
prolong REM sleep
 small lesions ventral to LC selectively abolish REM muscle atonia

27. The Executive Mechanism
 Peribrachial area:
 The region around the brachium conjunctivum, located in the dorsolateral pons;
contains acetylcholinergic neurons involved in the initiation of REM sleep.
 Carbachol:
 A drug that stimulates acetylcholine receptors.

28.  Medial pontine reticular formation (MPRF):
 A region that contains neurons involved in the initiation of REM sleep;
activated by acetylcholinergic neurons of the peribrachial area.
 Magnocellular nucleus:
 A nucleus in the medulla; involved in the atonia (muscular paralysis) that
accompanies REM sleep.

29. For you to sleep well at night, the aesthetic, the quality, has
to be carried all the way through… (Steve Jobs)
• Have a nice sleep!