PSY3349 Sleep and Sleep Disorders
TASK 1 – QUALITY AND QUANTITY
SLEEP AND BIOLOGICAL RHYTMS
Source: Carlson (2014)
Neuromodulators influencing sleeping and waking
Adenosine
One study suggested that adenosine (a nucleoside neuromodulator) might play a primary role in the
control of sleep. Astrocytes maintain a small stock of nutrients in the form of glycogen, an insoluble
carbohydrate that is also stocked by the liver and the muscles. In times of increased brain activity this
glycogen is converted into fuel for neurons; thus, prolonged wakefulness causes a decrease in the level
of glycogen in the brain. A fall in the level of glycogen causes an increase in the level of extracellular
adenosine, which has an inhibitory effect on neural activity. This accumulation of adenosine serves as
a sleep-promoting substance. During slow-wave sleep, neurons in the brain rest, and the astrocytes
renew their stock of glycogen. Caffeine blocks the adenosine receptors, preventing the inhibitory
effect on neural activity and reducing the effects of sleep deprivation
Acetylcholine
Circuits of neurons that secrete at least five different
neurotransmitters play a role in some aspect of an
animal’s level of alertness and wakefulness (commonly;
arousal). One of the most important neurotransmitters
involved in arousal is acetylcholine (ACh). Two groups
of acetylcholinergic neurons, one in the pons and one
located in the basal forebrain, produce activation and
cortical desynchrony when they are stimulated. A third
group, located in the medial septum, controls the activity
of the hippocampus.
Acetylcholinergic agonists increase EEG signs of
cortical arousal, whereas ACh antagonists decrease
them.
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Norepinephrine
Catecholamine agonists such as amphetamine produce arousal and sleeplessness. These effects
appear to be mediated primarily by the noradrenergic system of the locus coeruleus (LC), located in
the dorsal pons. Neurons of the LC give rise to axons that branch widely, releasing norepinephrine
(from axonal varicosities) throughout the neocortex, hippocampus, thalamus, cerebellar cortex, pons,
and medulla; thus, they potentially affect widespread and important regions of the brain.
One study recorded the activity of noradrenergic
neurons of the LC across the sleep-wake cycle in
rats. They found that this activity was closely
related to behavioral arousal; the firing rate of
these neurons was high during wakefulness, low
during slow-wave sleep, and almost zero during
REM sleep (figure). Most investigators believe
that activity of noradrenergic LC neurons
increases an animal’s vigilance; its ability to pay
attention to stimuli in the environment. Figure;
activity of noradrenergic neurons in the locus
coeruleus.
Serotonin
Serotonin (5HT) also appears to play a role in activating behavior. Almost all of the brain’s
serotonergic neurons are found in the raphe nuclei, which are located in the medullary and pontine
regions of the reticular formation. The axons of
these neurons project to many parts of the brain,
including the thalamus, hypothalamus, basal
ganglia, hippocampus, and neocortex.
Stimulation of the raphe nuclei causes
locomotion and cortical arousal (as measured by
the EEG), whereas PCPA, a drug that prevents
the synthesis of serotonin, reduces cortical
arousal. Figure; activity of serotonergic neurons
in the dorsal raphe nuclei.
Histamine
The fourth neurotransmitter implicated in the control of wakefulness and arousal is histamine, a
compound synthesized from histidine, an amino acid. The cell bodies of histaminergic neurons are
located in the tuberomammillary nucleus (TMN) of the hypothalamus, located at the base of the
brain just rostral to the mammillary bodies.
The axons of these neurons project primarily to the cerebral cortex, thalamus, basal ganglia, basal
forebrain, and other regions of the hypothalamus. The projections to the cerebral cortex directly
increase cortical activation and arousal, and projections to acetylcholinergic neurons of the basal
forebrain and dorsal pons do so indirectly, by increasing the release of acetylcholine in the cerebral
cortex.
The activity of histaminergic neurons is high during waking but low during slow-wave sleep and REM
sleep. Although histamine clearly plays an important role in wakefulness and arousal, evidence
suggests that control of wakefulness is shared with the other neurotransmitters discussed before.
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Orexin
The cause of narcolepsy is degeneration of orexinergic neurons in humans and a hereditary absence of
one type of orexin receptors in dogs. The cell bodies of neurons that secrete orexin are located in the
lateral hypothalamus. Although there are only about 7000 orexinergic neurons in the human brain,
the axons of these neurons project to almost every part of the brain, including the cerebral cortex and
all of the regions involved in arousal and
wakefulness, including the locus coeruleus,
raphe nuclei, tuberomammillary nucleus,
and acetylcholinergic neurons in the dorsal
pons and basal forebrain. Orexin has an
excitatory effect in all of these regions.
Figure; activity of single orexinergic neurons
during various stages of sleep and waking.
Summary of neurochemical levels involved in regulation of sleep/wake cycle
Neural control of slow-wave sleep
If we go without sleep for a long time, we will eventually become sleepy, and once we sleep, we will
be likely to sleep longer than usual and make up at least some of our sleep debt. This control of sleep
is homeostatic in nature. But under some conditions, it is important for us to stay awake, for example,
when we are being threatened by a dangerous situation or when we are dehydrated and are looking for
some water to drink. This control of sleep is allostatic in nature, a term that refers to reactions to
stressful events in the environment (danger, lack of water) that serve to override homeostatic control.
Finally, circadian factors, or time of day factors, tend to restrict our period of sleep to a particular
portion of the day/night cycle.
The primary homeostatic factor that controls sleep is the presence or absence of adenosine, a chemical
that accumulates in the brain during wakefulness and is destroyed during slow-wave sleep. Allostatic
control is mediated primarily by hormonal and neural responses to stressful situations and by
neuropeptides (such as orexin) that are involved in hunger and thirst.
The level of brain activity is largely controlled by the five sets of arousal neurons. A high level of
activity of these neurons keeps us awake, low levels put us to sleep. But what controls the activity of
the arousal neurons?
The preoptic area, the region of the anterior hypothalamus, is an area most involved in control of
sleep. The preoptic area contains neurons whose axons form inhibitory synaptic connections with the
brain’s arousal neurons. When our preoptic neurons (‘sleep neurons’) become active, they suppress
the activity of our arousal neurons, and we fall asleep. The majority of the sleep neurons are located in
the ventrolateral preoptic area (vlPOA).
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