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Neurons (nerve cells) in the brain and
brainstem produce a variety of nerve-signalling
chemicals called neurotransmitters in different
parts of the brain. These neurotransmitters in
turn act on different groups of neurons in
various parts of the brain, which control
whether we are asleep or awake. the timing of
the activation of these various different
processes results from the interaction between
the increasing homeostatic drive to sleep and
the changing influence of our internal circadian
| clock.
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[A ie — a oe — Se
In general, when the alerting areas of the brain are
most active, they send arousalsignals to the
cerebral cortex (the outer layer of the brain that is
responsible for learning, thinking, and organizing
information), while at the same time inhibiting
activity in other areas of the brain that are
responsible for promoting sleep, resulting in a
period of stable wakefulness. When the sleep-
promoting areas of the brain are most active, on
the other hand, they inhibit activity in areas of the
brain responsible for promoting wakefulness,
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الك ae ل +78
i It used to be thought that the brain had a
#8 specific “sleep centre” (in the hypothalamus)
and a separate “wakefulness centre” (in the
= reticular activating system in the brainstem),
but more recent research has indicated that the
situation is actually substantially more
complicated than that: wakefulnessactually
4 appears to be regulated by a whole network of
redundant structures in the brainstem,
۱ hypothalamus and basal forebrain, and is not
centred in any one part of the brain.
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=
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i | سم “ §
The ventrolateral preoptic nucleus (VLPO or VLPN) of
the hypothalamus is one area of the brain that is
particularly involved in the switch between
wakefulness and sleep. Neurons in this small area
help to promote sleep by inhibiting activity in areas
of the brainstem that maintain wakefulness.
Likewise, in a process of “mutual inhibition”, during
waking hours, those areas of the brain that are
active in maintaining wakefulness by stimulating the
cerebral cortex also work to inhibit the neurons of
the VLPO. For this reason, the VLPO is often referred
to as the “sleep switch”, although this is really a
gross simplification.
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۱۳۳ A 200000 د١ )ذا مث 2 ىد ال -
۳ A whole cocktail of neurotransmitters are involved in driving
wakefulness and sleep, including histamine, dopamine, norepinephrine,
_ serotonin, glutamate, orexin and acetylcholine, among others. While
none of these neurotransmission processes is individually necessary,
they all appear to contribute in some way. Histamine in particular is
sometimes referred to as the “master” wakefulness-promoting
neurotransmitter, exhibiting high activity during wakefulness,
decreasing activity during non-REM sleep, and its lowest levels during
REM sleep(which is why histamine-blocking antihistamine medications
cause drowsiness and increase non-REM sleep). Serotonin activity
promotes wakefulness, increases sleep-onset latency (the length of
time it takes to fall asleep) and decreases REM sleep.
Acetylcholineactivity in the reticular activating systemof the brainstem
stimulates activity in the forebrain and cerebral cortex, encouraging
alertness and wakefulness, although it also appears to be active during
REM sleep. Dopamine activity sometimes seems to promote
wakefulness and sometimes sleep (it is also involved in the process of
dreaming), so its role is still far from clear.
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When sleep is called for, the normal signals of wakefulness
are interrupted at the thalamus, which serves as the
“gatekeeper” to the cerebral cortex (the furrowed outer
layer of the brain where most conscious activity takes
place), effectively disconnecting the cortex from most
internal and external signals. Another neurotransmitter,
serotonin, is also released in the brain throughout the day,
which has the effect of stimulating a particular area in the
hypothalamus, which in turn inhibits a different part of the
same organ, all of which has the effect of encouraging «
sleep. Even more importantly, serotonin is used by the
body to produce yet another hormone, melatonin,
sometimes called the “ sleep hormone”, which is a major
regulator our biological or circadian clock.
- Fe _ 535 - ۲ و —— « - id
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Melatonin ee increases in
‘causing drowsiness and helping to lo
then decreases back to its normal negligibl
۱۹۸2۸ ning.General anesthetics pro a widespread
یو ion in the central nervous system by enhancing
121 neurotransmission and reducing excitatory
neurotransmission. However, the action mechanisms of general
يا are not completely understood. Moreover, the
tate comprises multiple components
ل i and immobility), each of
Bi is mediated by different receptors and neuronal pathways.
4
Recently, neurotransmitter- and voltage-gated ion channels have
emerged as the most likely molecular targets for general
anesthetics. The y-aminobutyric acid type A (GABAA) receptors
are leading candidates as a primary target of general
iil
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ی ات ااه ..... م
It has been conventionally known that general
anesthetics act on CNS non-specifically. However, there
has recently been much progress in understanding the
functional mechanisms, as well. Most of the general
anesthetics act on various neurotransmitter-gated ion
channels. The most known representative target is the
GABAA receptor. Especially thanks to the advancement
in genetic engineering, the ways in which various
behavioral response patterns are selectively related to
the GABAA receptor subunits in specific parts of the
brain have been gradually revealed. Such progress not
only increases the understanding of the mechanisms of
general anesthetics, but also provides help in
developing novel and selective anesthetics.
