BRAIN : THE MASTER

SLEEP / WAKE

TYPES OF SLEEP

WAKE-PROMOTING AREAS

SLOW-WAVE SLEEP AREAS

REM SLEEP AREAS

Ananya Chowdhury
M.Sc Life Sciences
2nd Semester
J.N.U
BRAIN : THE MASTER
Head of the family
Controls every function of the body
Different parts, different jobs, still work together in harmony
Major parts of brain:
1) Forebrain- i) cerebral cortex
ii) hippocampus
iii) basal ganglion
iv) limbic system
v) thalamus
vi) hypothalamus
2) Midbrain
3) Hindbrain- i) cerebellum
ii) pons
iii) medulla oblongata
BRAIN : THE MASTER
BRAIN : THE MASTER
Another way of division of brain:
1) Cerebrum- i) cerebral cortex
ii) basal ganglion
iii) thalamus
iv) hypothalamus
v) limbic system
2) Cerebellum
3) Brain Stem- i) midbrain
ii) pons
iii) medulla
Afferent/Ascending projections- carry information towards higher
centres of brain
Efferent/Descending projections- carry information away from
higher centres of brain
Sleep / Wake
Sleep: Physiological,reversible state of body with reduced
voluntary body movements and decreased awareness of the
surroundings.
Restorative process of the body
Wakefulness is associated with heightened neuronal activity in
brain, increased muscle activity of body and intensified mental
activity.
After a certain period of arousal, the entire body and mind gets
tired and sleep initiates.
Good sleep MAKES A MAN HEALTHY, WEALTHY AND WISE
TYPES OF SLEEP
Two types of sleep: i) Non-REM
ii) REM
Aserinsky gave the concept of Rapid Eye Movement (REM) Sleep in 1953
Features: i) low amplitude and high frequency desynchronised waves (>12 Hz)
ii) muscle atonia
iii) EOG singlets and clusters
iv) Hippocampal theta waves (4-9 Hz)
v) PGO (Pontine geniculate occipital) spikes
vi) flactuations in blood pressure, heart rate, body temperature
Dement gave 4 different stages of NREM sleep in humans according to EEG
activity
1) Stage1 : 8-12 Hz, alpha and theta waves.
2) Stage2 : 4-8 Hz, theta waves.
3) Stage3 : 2-4 Hz, delta (20-50%) and theta waves.
4) Stage4 : 0.5-2 Hz, delta (more than 50%) and theta waves.
The Stages 3 and 4 were specifically called Slow Wave Sleep (SWS)
WAKE-PROMOTING AREAS
WAKE-PROMOTING AREAS
When a person is awake, his attention is directed to some specific type
of mental activity, several neurons fire together but often nullify each
other in the recorded brain waves; giving rise to desynchronized low
amplitude high frequency beta waves (14-80 Hz)
Requires steady flow of ascending impulses arising in the brain stem ;
ARAS ( Ascending reticular activating system ) localized within the
core of pons and midbrain
Studied by i) lesion studies damaging the cells of particular area
electrically or chemically
ii) single cell recording to identify particular group of
neurons that increase/ decrease firing
iii) application of agonist ( enhance the effect of the
neurotransmitter ) and antagonist (block the action of the
neurotransmitter)
WAKE-PROMOTING AREAS
In ARAS:
1) LOCUS COERULUS (LC) : Norepinephrine
2) RAPHE NUCLEUS (RN) : Serotonin
3) PEDUNCULOPONTINE TEGMENTUM (PPT) : Acetylcholine
4) MIDBRAIN RETICULAR FORMATION (MRF) : Glutamate
5) SUBSTANTIA NIGRA (SNc) , VENTRAL TEGMENTAL AREA (VTA): Dopamine
Projections from these areas travel dorsally to activate THALAMO-CORTICAL system
as well as ventrally to activate HYPOTHALAMO-CORTICAL and BASALO-CORTICAL
systems.
In addition, some parts of forebrain promote wakefulness independently or in
coordination with ARAS:
1) POSTERIOR HYPOTHALAMUS (PH) : Histamine
2) LATERAL HYPOTHALAMUS (LH) : Hypocretin (orexin)
3) BASAL FOREBRAIN (BF) : Acetylcholine
4) SUPRACHIASMATIC NUCLEUS (SCN)
5) PREFRONTAL CORTEX (PFC)
SLOW-WAVE SLEEP AREAS
SLOW-WAVE SLEEP AREAS

During wakefulness, there is slow accumulation of

i) metabolites like Adenosine
ii) inhibitory amino acids like GABA and glycine
iii) prostaglandin PGD2
iv) cytokines like interleukin1beta and tumor necrosis factor alpha
These facilitates the transition from wakefulness to sleep when accumulated
sufficiently in CSF.
SWS is generated via the activation of GABAergic and Galanin synthesizing
neurons in Pre Optic Area (POA) of the Anterior Hypothalamus.
These GABAergic neurons innervate and inhibit wake-promoting centres both
by
i) Descending projections to Posterior Hypothalamus (HA), Substantia nigra
(DA), Lateral Hypothalamus (Hcrt), Midbrain Reticular Formation (Glut), Raphe
nucleus (5-HT), PedunculoPontineTegmentum (Ach) and Locus Coerulus (NE)
ii) Ascending projections to Basal Forebrain (Ach), SCN, mPrefrontalCortex
In addition, increased activity of GABAergic cells in layers I and II of the cortex
and solitary nucleus also contribute to maintainence of SWS.
REM SLEEP AREAS
Reciprocal-interaction model (Hobson and Mc Carley)

i) REM-ON cells of median pontine reticular formation

(mPRF) are CHOLINERGIC
Ii) REM-OFF cells are AMINERGIC (noradrenergic in LC and
serotonergic in DR)
During Wake, aminergic REM-OFF cells are activated,
inhibiting the cholinergic REM-ON cells.
During Non-REM sleep, aminergic inhibition goes down
gradually
At the onset of REM sleep, aminergic inhibition turned off
and REM-ON cells are active.
REM SLEEP AREAS
Bernard et al identified cholinergic cells in LDT/PPT areas instead of mPRF, so
new location for REM-ON cells shifted to LDT/PPT.

But injecting noradrenergic agonists into LDT/PPT areas did not inhibit REM
sleep, putting Reciprocal-Interaction into doubt.

Found kainate receptors on the cholinergic cells, activated by GLUTAMATE.

So, 1) Glutamate activated cholinergic REM-ON cells to release acetylcholine in
the REM sign generators.
2) As LDT/PPT cholinergic cells are activated, local GABAergic cells in LC and
RN are activated, inhibiting the REM-OFF cells.
During wake, the activity of both aminergic and cholinergic cells are high
With SWS, equal reduction in both, still proportionate
During REM, aminergic cells have reduced activity while cholinergic cells are
relatively high., turning on the REM Sign-generators.
REM SIGH GENERATORS
REM SIGN-GENERATORS
Each individual sign of REM sleep is executed by increased
activation of distinct cell groups in the brain stem.
1) Midbrain reticular formation (MRF), medullary magnocellular
nucleus(MMN) : Cortical EEG
2) Locus Coerulus Alpha (LC a) : Muscle atonia
3) Peri-Abducens reticular formation (PAb) : Rapid Eye Movement
4) Caudo-Lateral Peribrachial area (C-PBL) : PGO waves
5) Pontis Oralis (PO) : Hippocampal Theta waves
6) Parabrachial nucleus (PBN) : Autonomic flactuation of Blood
pressure, heart rate, Body temp, respiration