SLEEP & ALERT BEHAVIOUR

(RETICULAR FORMATION &

THALAMUS)
LEARNING OUTLINE
Thalamus and its functions
Reticular formation: components, functions, reticular pathways and
ascending reticular activating system (ARAS)
Electrical activity of brain**
Wakefulness: components and neurotransmitters involved with their
roles**
Sleep-wake cycle***
Applied physiology
THALAMUS
It is the large collection of neuronal groups within diencephalons;
participates in sensory, motor and limbic functions.
Gateway to the cerebral cortex because all information that reaches
cortex is processed by thalamus
Divided into nuclei that project diffusely wide to wide regions of
neocortex (the midline and intralaminar nuclei) and nuclei that project
to specific discrete portions of neocortex and limbic system (the
specific sensory relay nuclei and nuclei concerned with efferent
control mechanisms).
RETICULAR FORMATION
There are cell groups in the core of the brainstem that constitute brain stem reticular formation.
Formed by a diffuse systems of neurons having widely branching axons.
These neurons having very long dendrites and axons.
They have long ascending branches projecting to the thalamus and cortex and long descending
branches projecting to the spinal cord.
RETICULAR FORMATION
(CONTINUED)
The neurons are organized into 2 columns:
Medial columns
-Medial group of cells constitute gigantocellular part(large cell group) which cotain the raphe nuclei
and central group of nuclei.
-Receive afferents from all sensory pathways, especially from spinoreticular tract.
-Fibers fro this part project upward as the RAS.They project downward as the medial and lateral
reticulospinal tract.

Lateral Columns
-Laterally placed is the parvocellular part containing small-cell nuclei
-Contribute to sleep-wakefulness
COMPONENTS OF RAS
1.Ascending reticular activating neurons

-Maintain arousal of being

-Increase activity causes by excitation of cortical neurons and creates alertness
and wakeful state
-Decrease activity induces sleep
2. Monoaminergic and cholinergic fibers
-Involved in itegration of various sensory and behavioral activity

3.Fibers from parvocellular tract

-active only during the awaken state and silent during sleep.

4.Serotonergic neurons
-Originating from raphe nuclei project to all part of CNS
-Active during deep sleep
-This indicates that these neurons are involved in genesis of sleep
-Histaminergic neurons projecting from hypothalamus to all parts of CNS and plays major ole in arousal.
FUNCTIONS OF RETICULAR FORMATION
1)Control of motor activities
-regulation of posture

2)Control of sensory activities

-pain sensation

3)Controls of Cardiovascular and Respiratory

4)Control of visceral function

-vomiting and swallowing reflexes are integrated in medullary reticular
formation.

5)Sleep and wakefulness.

EVOKED CORTICAL POTENTIAL
SECONDARY DIFFUSE
PRIMARY EVOKED POTENTIAL
POTENTIAL
Highly specific in its location Not highly localized.
Latency 5-12 ms Appears at the same time of the
most of the cortex
Latency 20-80 ms
PHYSIOLOGICAL BASIS OF
ELECTROENCEPHALOGRAM
Electroencephalogram is the record of variations in brain
potential.
EEG can be recorded with scalp electrodes through the
unopened skull or with electrodes on or in the brain.
Electrocorticogram (ECoG) is used for the record
obtained with electrodes on the pial surface on the
cortex.
EEG records bipolar or unipolar
 Bipolar records show fluctuations in the potential difference
between two cortical electrodes
 Unipolar records show the potential difference between a
cortical-electrode and a theoretically indifferent electrode on
some part of the body distant from the cortex.
ELECTRICAL ACTIVITY OF BRAIN
APPLIED PHYSIOLOGY: EPILEPSY
WAKEFULNESS: COMPONENTS &
NEUROTRANSMITTERS
Components
 ascending reticular activating system. Comprises of 2 branches:
1st branch: innervate the thalamus. Activating relay neuron and
reticular nuclei. Consist of cholinergic neurons; pedunculopontine
nucleus (PPN) and the laterodorsal tegmental nucleus (LDT) (Ach)
2nd branch: projects into the lateral hypothalamus, basal forebrain,
and the cerebral cortex. Consist of monoaminergic
structures histamine, serotonin , dopamine, norepinephrine &
melatonin.
NEUROTRANSMITTERS AND ITS
ROLES
Cholinergic (Ach) : highest when in an awake state but also active during
REM sleep, and is minimal in non-REM sleep
Histamine ; “master” wakefulness-promoting neurotransmitter, exhibiting
high activity during wakefulness, decreasing activity during non-REM sleep,
and its lowest levels during REM sleep
Serotonin ; promotes wakefulness, increases sleep-onset latency (the length
of time it takes to fall asleep) and decreases REM sleep.
Dopamine ; sometimes seems to promote wakefulness and
sometimes sleep (it is also involved in the process of dreaming- still unclear)
orexin (hypocretin); Activation triggers wakefulness, while low levels at
night serve to drive sleep. Also regulates arousal & appetite. A deficiency
results in sleep-state instability, leading to many short awakenings and
mixed-up REM and non-REM sleep states typical of sleep
disorders like narcolepsy.
REGULATOR OF
SLEEP WAKE CYCLE
• Brain stem RAS release nor
epinephrine & serotonin or
acetylcholine
• Preoptic neuron in hypothalamus
release GABA
• Posterior hypothalamic neuron
release histamine
• Oresin produce in hypothalamic
neuron
• This secretions are important in
switching between sleep and
wakefulness
When activity of norepinephrine & serotonin increases, the activity of
acethylcholine decreases causing awake state
Reverse this pattern cause REM sleep
NREM sleep are control by aminergic n cholinergic neuron
Increase of GABA and reduce histamine lead to NREM sleep, via
deactivation of thalamus and cortex.
The reverse of this pattern is awake state.
Besides that, melatonin play a role by inhibiting adrenaline cyclase
resulting in sleepness (MT 1 receptor)
FACTORS AFFECTING SLEEP
Light's Effect
Light exposure can cause our biological clock to advance or delay, which affects our sleep
and wake cycle.
Light is one of the most important external factors that can affect sleep. It does so both
directly, by making it difficult for people to fall asleep, and indirectly, by influencing the
timing of our internal clock and thereby affecting our preferred time to sleep.

Jet Lag and Shift Work

Normally, light serves to set our internal clock to the appropriate time.
However, problems can occur when our exposure to light changes due to a
shift in work schedule or travel across time zones.
Under normal conditions, our internal clock strongly influences our ability to
sleep at various times over the course of a 24-hour period, as well as which
sleep stages we experience when we do sleep.
Pain, Anxiety, and Other Medical Conditions
A wide range of medical and psychological conditions can have an impact on the structure and distribution of
sleep.
Individuals of all ages who experience stress, anxiety, and depression tend to find it more difficult to fall
asleep, and when they do, sleep tends to be light and includes more REM sleep and less deep sleep.
Medications and Other Substances
Many common chemicals affect both quantity and quality of sleep. These include caffeine,
alcohol, nicotine, and antihistamines, as well as prescription medications including beta
blockers, alpha blockers, and antidepressants.
The Sleep Environment
Light and temperature effect the quality and restfulness of your sleep.
The bedroom environment can have a significant influence on sleep quality and quantity.
Several variables combine to make up the sleep environment, including light, noise, and
temperature.
TYPES AND STAGES OF SLEEP
•Sleep architecture refers to the basic structural organization of normal sleep.
•There are two types of sleep, non-rapid eye-movement (NREM) sleep and rapid eye-
movement (REM) sleep
•NREM sleep is divided into stages 1, 2, 3, and 4 and each has its own unique characteristics
including variations in brain wave patterns, eye movements, and muscle tone.
•Sleep cycles and stages were uncovered with the use of electroencephalographic (EEG)
recordings that trace the electrical patterns of brain activity
A sleep episode begins with a short period of NREM stage 1
progressing through stage 2, followed by stages 3 and 4 and finally
to REM.
However, individuals do not remain in REM sleep the remainder of the
night but, rather, cycle between stages of NREM and REM throughout
the night.
NREM sleep constitutes about 75 to 80 percent of total time spent in
sleep, and REM sleep constitutes the remaining 20 to 25 percent
STAGES OF SLEEP AND SLEEP
CYCLE
4 STAGES OF NREM SLEEP
Stage 1 Sleep
NREM stage 1 sleep serves a transitional role in sleep-stage cycling.
This stage usually lasts 1 to 7 minutes in the initial cycle, constituting 2 to 5 percent of total sleep,
and is easily interrupted by a disruptive noise. Brain activity on the EEG in stage 1 transitions
from wakefulness to low-voltage, mixed-frequency waves.
Stage 2 Sleep
Stage 2 sleep lasts approximately 10 to 25 minutes in the initial cycle and lengthens with
each successive cycle, eventually constituting between 45 to 55 percent of the total sleep
episode. An individual in stage 2 sleep requires more intense stimuli than in stage 1 to
awaken. Brain activity on an EEG shows relatively low-voltage, mixed-frequency
activity characterized by the presence of sleep spindles and K-complexes.
Sleep spindles are important for memory consolidation. Individuals who learn a new task
have a significantly higher density of sleep spindles than those in a control group
Stages 3 and 4, Slow-Wave Sleep
Sleep stages 3 and 4 are collectively referred to as slow-wave sleep, most of which
occurs during the first third of the night. Each has distinguishing characteristics.
Stage 3 lasts only a few minutes and constitutes about 3 to 8 percent of sleep. The
EEG shows increased high-voltage, slow-wave activity.
The last NREM stage is stage 4, which lasts approximately 20 to 40 minutes in the
first cycle and makes up about 10 to 15 percent of sleep. The arousal threshold is
highest for all NREM stages in stage 4. This stage is characterized by increased
amounts of high-voltage, slow-wave activity on the EEG
EEG READING SHOWING STAGES
OF SLEEP
REM Sleep
REM sleep is defined by the presence of desynchronized (low-voltage, mixed-
frequency) brain wave activity, muscle atonia, and bursts of rapid eye movements.
During the initial cycle, the REM period may last only 1 to 5 minutes; however, it
becomes progressively prolonged as the sleep episode progresses.
Dreaming is most often associated with REM sleep. Loss of muscle tone and
reflexes likely serves an important function because it prevents an individual from
“acting out” their dreams or nightmares while sleeping.
VARIATION IN SLEEP CYCLE &
TOTAL DURATION OF SLEEP
Average sleep time per day
- infancy 16 hrs ( 50% of sleep in REM )
-childhood 10hrs ( 2hrs REM & 8hrs REM)
-adulthood 10hrs ( 2hrs REM & 6hrs NREM)
-old age less than 8 hrs ( slow wave sleep no longer present in man)
PHYSIOLOGICAL SIGNIFICANCE
OF SLEEP
Sleep serve as a period of body’s rest and metabolic restoration
- During non-REM
- Release of growth hormone and gonadotrophin
- Decrease in blood pressure, heart rate and respiratory rate

Sleep is important for mental wellbeing

-During REM
-Dreaming (Brain is highly active)
-Long term chemical and structural changes for learning and memory
INSOMNIA
DEFINITION
Insomnia is defined by having difficulty falling asleep, maintaining sleep, or by
short sleep duration, despite adequate opportunity for a full night’s sleep. Other
insomnia symptoms include daytime consequences, such as tiredness, lack of
energy, difficulty concentrating, and/or irritability .
The diagnostic criteria for primary insomnia include:-

-Difficulty initiating or maintaining sleep or nonrestorative sleep.

-Causing clinically significant distress or impairment in social, occupational, or
other important areas of functioning.
MECHANISM OF INSOMNIA
The causes of insomnia are poorly understood but, in generally it involve a
combination of biological, psychological, and social factors. Insomnia is
conceptualized as a state of hyperarousal. Stress is thought to play a leading
role in activating the hypothalamic pituitary axis and setting the stage for
chronic insomnia. A key study showed that adults with insomnia, compared
with normal sleepers, have higher levels, over a 24-hr period, of cortisol and
adrenocorticotropic hormone (ACTH), which are hormones released by the
hypothalamic pituitary adrenal axis after stress exposure. The 24 hour pattern
of cortisol and ACTH secretion is different, however, from that in individuals
who are chronically stressed.
NARCOLEPSY
DEFINITION
Narcolepsy is a neurological disorder caused by the brain's inability to regulate sleep
wake cycles normally. The main features of narcolepsy are fatigue and cataplexy.

MECHANISM OF NARCOLEPSY
all individuals who suffer narcolepsy with cataplexy carry the haplotype HLA-DQB1*0602
and have severe neuronal loss in regions of the brain that are responsible for regulating
the sleep-wake cycle. Approximately 70,000 hypothalamic neurons that are responsible
for producing the neuropeptide hypocretin (orexin) are lost in individuals with narcolepsy
with cataplexy. Hypocretin is an excitatory neuropeptide that regulates the activity of
other sleep regulatory networks. Consequently,in some cases low levels of hypocretin-1
in the CSF, may be used to diagnose narcolepsy.The cause of hypocretin cell loss is
unknown but it may be autoimmune due to the association with the HLA-DQB1*0602.
SLEEP
WALKING/SOMNAMBULISM
Awake:
 Brain waves are fine and choppy when we’re awake,
Sleep:
 Brain waves get slower, bigger, and more synchronized.
Sleepwalking:
 Occurs during deep sleep, stages 3 and 4, where brain waves are the slowest and biggest.
(Carthill)
 Sleepwalking as an Altered State :
Although sensory mechanisms are necessary for consciousness, we can still perceive and
therefore respond to them without being aware of them. (Carthill)
The best example of this is sleepwalking.

 Causes :
Disturbed Sleep Cycle (Epsa, 2000)
 More Common in Children (15% experience at least one episode)
 Genetics (HLA)
 Extreme Stress, Sleep Deprivation
 Personality Disorders (Aggression)
 Diurnal Variation in Plasma Vasopressin
(p-AVP)

This slide illustrates the diurnal variation in plasma vasopressin secretion

between nocturnal enuretics and normal children. Enuretic children have
much lower levels of plasma vasopressin between 22:00 hrs and 06:00 hrs
than normal children; whose vasopressin secretion increases at night.
 Urine Urine
production rate osmolality

This slide illustrates the findings of Rittig et al. (1989). This controlled study
compared the rate of urine production and urine osmolality in enuretic and
normal children. Normal children demonstrated a greater decrease in urine
production from day to night which often resulted in a significant increase in
urine osmolality. Enuretic children did not display significant changes in urine
production or urine osmolality between day and night