NEUROBIOLOGY OF SLEEP

Consciousness 00:01:500

Consiousness has a parts :

LArousal sustem: Person can respond to external stimulus.

* is maintained by a structures

621345ea7912tda82baso9 reticular activating sustem

Thalamus
a.Content of Consiousness
t is maintained by

Cortex
Thalamus

Arousal response:
Is a primitive response needed for survival
Any response for survival comes rom the brain stem,
Sub-cortical structures like thalamus and basal
ganglia.
Autonomic survivals for
ight and Aght response is requlated
by the hypothalamic limbic system but orignates from the
oLutonomic nucleus in the brain stem
The conscious content in a new bom baby is minimal t
improves over time with the maturity of the cortex

Ascending reticular activating system (ARAS) 00:05:18

Reticular activoting sustem are large number of nucleus

uhich is locoted in the brain stem, predominantly in the pons.
t sends connection upuwards to the sub-cortical structures.
This is called as ARAS.
Simutaneouslu, it sernds connection dounuuards to the spinal
cord motor neurons. Ht goes via the medulla or the pons
medullaruy: Lateral andinhibitory
Pontine medial and stimulatory,
Thalamus
t is the qateuay to the brain.
All the inputs from the peripheral systerm travels via the
thalamus.
Ht has mutiple nucleus Anterior nucleus, dorsomedial nucleus,
ventrolateral nucleus.
Different inputs come through different nucleus, and these
are projected to the cortex.
This is Knoun as thalamocortical pathway.
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t is an activatina pathway and maintains concsiousness.

The nucleus reticularis thalamus (N2T) :

Specitc role.
The only nucleus in thalamus which is inhibitory and does not

project the inputs to the cortex

The inputs are projected to other thalamic nucleus.
As it inhitbits the thalamus; the thalamocortical activation

tails, producing sleep or decrease in arousal

EEG shows sunchronisation: The different areas in the brain
have similar morphology and requency (same wave pattern.

ARAD
L ARAS inhibit NRT.
Thalamus activates the cortex
As a resut of which, the person is awake.

eEa shouws desynchronisation.

a. ARAS also has an extrathalamic pathuay
This projects to the eBasal forebrain and Hypothalamu

Basal forebrain 00:14:40

In the basal area of the brain near the anterior pertoratin

substance there are certain nucleus (arey mattern.
different types of rucleus.
Basal forbrain is the collection o#
For example: nucleus Accubens, nucleus basalis of meynret,

diagonal band of eroca

There are 3 neurotrsansmitters in the basal forebrain;
 Acetulcholine (most important).
Adenosine.
GneA/alutamate.

neurons in the basal forebrain activate the cortex.

Cholinerqic
This is siqnitcant as in the case of Alzheimer's diesease and

dementia, as the basal forbrain gets damaged

when the basal Porebrain neurons are less, the cortical

activation is decreased
This decreased cortical function is portrayed as cognitive

impairment or dementia.
used to
Cholineraic drugs ( Donepezil, memantine)
are

improve cognitive function.

secretes a hormone called Orexin.
Hupotthalamus
auuakeness.
plays a major role in
in the ARAS
activates the uake promoting regions located

Simutaneously it acitvates Rem oPt areas.

00:24:10
Arousal system

ARAS: Thalamic and extra thalamic.

Extra thalamic: Activate basal forebrain and posterior
hypothalamus.
and histamine.
Hypothalamus produces orexin
H containts NRT, Thalamus, ARAS.
NRT inhibits thalamus producing sleep.

wake promoting sustems

These include:
coeruleus).
. Non-adrenergic (orginates rom locus
a. seratonergic (orginates trom Raphae magnus)
The raphae magnus nucleus has
dorsal raphea and caucal
raphae. circuit
The dorsal raphae wdk qadatsrerdasvnas9upuward
and activation.
cord to
prodcue
The caudalraphae decends to the spinal
motor activity uwith arousal
rom ventrolateral periaqueductal
3. 0opaminergic (orginates
 gray/ventral teamental area).
rom the ventral teqmental orea in the midbrain, the
neurons will ascend to the cortex to form the mesolimbic
and mesocortical pathway This is Pormed by dopamine.
The mesocortical goes Prom the tegmenturm to the cortex
to activate the cortex. The mesolimbic qoes to the limbic
areas (behavioural response.
The ventroteamental pathuay is affected in dementia.
The mesocortical and mesolimbic sustem is involved in the
reuward pathuay
4. Glutamtatergie (orginates ¥rom parabra.chial nucleus).

s.Cholinergie (orginates from laterodorsal tegmentum and

pedunculopontine nucleus)
Activates Rem sleep
But in general waketullness.

Pedunculopontine nucleus is involved in the gait system.

. Orexinergic : Orexin huypocretin sustem (secreted Prom
lateral hypothalamus).
t is a moajor neurotransmitter involved in waketuliness
Orexin production is stimulated by ARAS.
7. Histaminergic neurons (located in the tuberomammillary

nucleus of the hypothalamus).

8. Others REm OFF, SCN Suprachiasmastic nucleus).
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00:30:58
Sleep promoting systems

L. ventrolateral preoptic nucleus (MPO) of hypothalamus.

Hupothalamus is involved in sleep and arousal.

LPO secretes GABA and galanine.
eoth are inhibitory,
(P2) located in the brain stem
a. Parafacial nucleus

t secretes GABA
Rem oN, melatonin.
3.Others
areas and wake promoting a r e a s are
The sleeP promoting
interlinked
Sleep wake suuitch Here when the activation of one side is
sliahtiy stronge, the weaker side has increased inhibition thus
further tipping the balance towards the stronger side.This
Wiplop switch allous for rapid state transitions.

621345ea7
-0opaminergce
Hupothalamus Secretes orexin-
Choinergie
- Ncradreraine
Seratogenic
slutaminerqic erainstem
H6taminergie

REM on and off 00:47:52

In uaketullness
Rem on
There are certain areas called Rem on which will suwitch on
Rem sleepP
This includes sub-locus cerleus which
produces Rem sleep.
Rem o
This area will inhibit the Rem on area.
Consists of veLAG and LOT.

Orexin
Activates the wake
promotina area.
The orexin is secreted
by the stimulation of ARAS in the
hypothalanmus
t inhibits Rem
In
cataplexuy orexin is less.
Insleep
it inhibits uwake prornoting
MPO When this is activated,

areas, as a resut
of uwhich ARAS is inhibited and orexin
secretion is decreased.

it inhibits Rem of neurons.

Indirectty and directy
Initial sleep is NREM
ARAS activation further
As the sleep progresses, orexin and
decreases leading to Rem sleep.

There are a swtiches

L Sleep-wuake switch.
a. NRem and Rem suwtich.
when the Rem on centre is activated, Rem sleep is initiated

which results in a things

LThe Rem on uill send an input upuuards to the basal

Forebrain (cholinergie neurons are activated).
when the cortex is activated in the basal torebrain by
the cholinergie sustem causes hypnopompic/hypnag90gjic
hallucinations or dreams.
a. t uwill send a stimulus to the spinal cord motor neurons
either directty or indirectly
Inhibition to the spinal cord produces Rem atony
In cases uhere atony is absent during Rem sleep, the
person starts enacting the dreams (as the muscles do
get paralysec).
This is Knoun as REm sleep behavioural disorder (RBD).
In cases uhere the orexin production is decreased, there
will be:
Decreased'letstätEHHAR72baB99d
Decreased Rem latency
Sleep attack/ Nlarcolepsy
The Rem on neurons are inhibited by Rem o.
Rem off is indirectiy under the control of vPO and orexin

system
 Thelamus

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motor
neuron