PHYSIOLOGY OF SLEEP

-Dr.M.Goutham Kiran
PG Resident
 CONTENTS

• Introduction
• REM Sleep
• NREM Sleep
• Stages of sleep
• Physiology of NREM sleep
• Physiology of REM sleep
• Circadian and homeostatic regulation of the sleep
• Circadian rhythms
• References
 INTRODUCTION

• Sleep is a fundamental behavior of all animal species

which occupies approximately one-third of human
lifespan.
• It is a state of decreased awareness of environmental
stimuli that is distinguished from states such as coma
or hibernation by its relatively rapid reversibility.
• Humans, like most other mammals, express two types
of sleep.
• It includes:
• REM Sleep (paradoxical sleep)
• NREM Sleep (orthodox sleep)
 REM SLEEP

• REM sleep derives its name from the frequent bursts of

eye movement activity that occur during sleep.
• It is also referred to as paradoxical sleep because the
electroencephalogram (EEG) during REM sleep is
similar to that of waking.
• In infants, the equivalent of REM sleep is called active
sleep because of prominent phasic muscle twitches.
 NREM SLEEP

• It is also called Orthodox sleep.

• It is characterized by decreased activation of the EEG.
• In infants it is called quiet sleep because of the relative
lack of motor activity.
 STAGES OF SLEEP

• For clinical and research applications, sleep is typically

scored in epochs of 30 seconds.
• Stages of sleep is defined by the visual scoring of three
parameters: EEG, EOG and EMG.
• When the eyes are closed in preparation for sleep,
alpha activity (8 to 13 Hz) becomes prominent,
particularly in the occipital regions.
• Sleep usually begins with stage N1 characterized by the loss of
alpha activity and the appearance of a low-voltage, mixed
frequency EEG pattern with prominent theta activity (4 to 7 Hz),
and occasional vertex sharp waves (V waves) over the central
regions.
• After a few minutes of stage N1, sleep progresses to stage N2
which is heralded by the appearance of sleep spindles (11 to 16
Hz, lasting ≥0.5 seconds) and K-complexes (high-amplitude,
negative sharp waves followed by positive slow waves) in the
EEG
• Stage N2 is generally followed by N3 which is a period
when 20 percent or more of each sleep epoch consists
of slow waves, that is, waves of 0.5 to 2-Hz frequencies
with peak-to-peak amplitudes of >75 μV over frontal
regions.
• N3 is also defined as slow wave sleep (SWS), delta
sleep, or deep sleep, because the arousal threshold
increases incrementally from stages N1 to N3.
• REM sleep, or stage R, is described in terms of tonic
(persistent) and phasic (episodic) components.
• Tonic aspects of REM sleep include the activated EEG
similar to that of stage N1, which may exhibit increased
activity in the theta band and a generalized decrease of
the tone of skeletal muscles except for the extraocular
muscles and the diaphragm.
• Phasic features of REM include irregular bursts of REMs and
muscle twitches.
 PHYSIOLOGY OF NREM SLEEP

• The EEG of NREM sleep is characterized by oscillatory

waveforms such as sleep spindles, K-complexes, slow
waves (0.5 to 2 Hz), and slow oscillations (mainly 0.7 to
1 Hz).
• Brain activation generally decreases in NREM sleep,
particularly slow wave sleep, which is characterized by
an overall decrease in cerebral blood flow
• The control of NREM sleep involves multiple structures
ranging from the lower brainstem through the
thalamus, hypothalamus, and forebrain.
• The generation of sleep oscillations requires the
interplay between intrinsic cellular properties and
synaptic activity mediated by cortico-cortical, cortico-
thalamo-cortical, and thalamoreticular loops.
• Work in animals has shown that, shortly before the
transition from waking to sleep, there is a change in
the firing mode of thalamic and cortical neurons.
• Thalamocortical cells are hyperpolarized, whereas
reticulothalamic cells are facilitated and further inhibit
thalamocortical cells, with the consequence that
sensory stimuli are gated at the thalamic level and
often fail to reach the cortex.
• Rebound firing due to the activation of intrinsic
currents in thalamocortical cells leads to the
emergence of oscillations in the spindle frequency
range.
• Slow oscillation is the result of a brief hyperpolarization
of cortical neurons.
• The hyperpolarization phase, also known as the down
state, is followed by a slightly longer depolarization
phase, known as the up state, during which the firing
of cortical neurons entrains and synchronizes spindle
sequences in thalamic neurons, resulting in EEG
detectable spindles.
• K-complexes are made up of the cortical depolarization
phase followed by its triggered spindles.
 NREM SLEEP NEUROCHEMISTRY

• Many substances modulate sleep, but no unique sleep

factor has been identified.
• GABA, the inhibitory neurotransmitter in the CNS,
appears to be majorly involved in thalamocortical
oscillations and in the inhibition of waking centers by
sleep-active cells.
• Most hypnotics, including barbiturates,
benzodiazepines, and several of the newer non-
• Adenosine, a degradation product of adenosine
triphosphate is a byproduct of brain metabolism
whose levels increase as a result of increased
glutamatergic activity.
• It accumulates in the basal forebrain and cerebral
cortex during prolonged wakefulness and decreases
during sleep.
 PHYSIOLOGY OF REM SLEEP

• In REM sleep, pons and caudal midbrain—are both

necessary and sufficient to generate the features of
REM sleep and represent the final common pathway for
the induction of REM sleep.
• Bilateral lesions within the pons and caudal midbrain
can completely eliminate REM sleep.
• Areas involved in REM sleep generation are
mesopontine tegmentum, thalamus, posterior cortical
areas, and limbic areas, which are highly activated
during REM sleep.
• Eye movements during REM sleep are tightly linked to
ponto-geniculo-occipital (PGO) waves and are
mediated by inputs to vestibular neurons that in turn
activate oculomotor cells.
• They originate from cholinergic burst cells in the
peribrachial region and are suppressed by serotonergic
cells in the raphe nuclei.
 CIRCADIAN AND HOMEOSTATIC
REGULATION OF SLEEP

• The regulation of sleep involves two key components- a

circadian and homeostatic component
• The circadian component is responsible for the change in
sleep propensity that is tied to the time of day.
• The homeostatic component refers to the fact that the
longer one stays awake, the greater the propensity to
sleep.
 THE TWO-PROCESS MODEL

• It is a model of sleep regulation positing a circadian

and a homeostatic process by Alexander A. Borbély
and his colleagues.
• It is based on the interaction between the homeostatic
process S and the circadian process C.
• Process S builds up across the day in response to the
increase in sleep pressure caused by wakefulness and
decreases during sleep.
• The circadian process C for sleep propensity, however,
reaches its peak during the latter half of the night.
Thus nocturnal sleep onset is primarily driven by
process S, whereas process C maintains sleep through
the latter part of the night.
 CIRCADIAN RHYTHMS

• The primary pacemaker for generating circadian

rhythms lies in the suprachiasmatic nucleus (SCN) of
the hypothalamus.
• The SCN regulates a number of neuroendocrine and
behavioral parameters, including sleep propensity as
measured by process C, to coordinate the state of the
organism with the 24-hour light–dark cycle.
• In lesions of the SCN, sleep is no longer concentrated
in one main episode but is dispersed across the entire
24-hour cycle.
• More recent studies have demonstrated that the
circadian timekeeping is more complex i.e. in addition
to the central pacemaker in the SCN, there are
peripheral clocks in many cells and organs.
 CONCLUSION

• The study of sleep has shed light on many aspects of

consciousness and the workings of the human brain.
• An appreciation of sleep neurobiology is essential for
clinicians, because psychiatric patients often have
sleep problems associated with their illnesses and most
psychiatric drugs have significant effects on sleep.
 REFERENCES

• Kaplan and Sadock’s comprehensive textbook of psychiatry-10th edition

• Kaplan and Sadock’s synopsis of psychiatry- 11th edition
THANK YOU