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= Reticular formation =
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Introduction
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The reticular formation is a set of interconnected nuclei that are
located throughout the brainstem. The reticular formation is not
anatomically well defined because it includes neurons located in
different parts of the brain. The neurons of the reticular formation
make up a complex set of networks in the core of the brainstem that
extend from the upper part of the midbrain to the lower part of the
medulla oblongata. The reticular formation includes ascending pathways
to the cortex in the ascending reticular activating system (ARAS) and
descending pathways to the spinal cord via the reticulospinal tracts.
Neurons of the reticular formation, particularly those of the
ascending reticular activating system, play a crucial role in
maintaining behavioral arousal and consciousness. The overall
functions of the reticular formation are modulatory and premotor,
involving somatic motor control, cardiovascular control, pain
modulation, sleep and consciousness, and habituation.
The modulatory functions are primarily found in the rostral sector of
the reticular formation and the premotor functions are localized in
the neurons in more caudal regions.
The reticular formation is divided into three columns: raphe nuclei
(median), gigantocellular reticular nuclei (medial zone), and
parvocellular reticular nuclei (lateral zone). The raphe nuclei are
the place of synthesis of the neurotransmitter serotonin, which plays
an important role in mood regulation. The gigantocellular nuclei are
involved in motor coordination. The parvocellular nuclei regulate
exhalation.
The reticular formation is essential for governing some of the basic
functions of higher organisms and is one of the phylogenetically
oldest portions of the brain.
Structure
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The human reticular formation is composed of almost 100 brain nuclei
and contains many projections into the forebrain, brainstem, and
cerebellum, among other regions. It includes the reticular nuclei,
reticulothalamic projection fibers, diffuse thalamocortical
projections, ascending cholinergic projections, descending
non-cholinergic projections, and descending reticulospinal
projections. The reticular formation also contains two major neural
subsystems, the ascending reticular activating system and descending
reticulospinal tracts, which mediate distinct cognitive and
physiological processes. It has been functionally cleaved both
sagittally and coronally.
Traditionally the reticular nuclei are divided into three columns:
* In the median column - the raphe nuclei
* In the medial column - gigantocellular nuclei (because of larger
size of the cells)
* In the lateral column - parvocellular nuclei (because of smaller
size of the cells)
The original functional differentiation was a division of caudal and
rostral. This was based upon the observation that the lesioning of the
rostral reticular formation induces a hypersomnia in the cat brain. In
contrast, lesioning of the more caudal portion of the reticular
formation produces insomnia in cats. This study has led to the idea
that the caudal portion inhibits the rostral portion of the reticular
formation.
Sagittal division reveals more morphological distinctions. The raphe
nuclei form a ridge in the middle of the reticular formation, and,
directly to its periphery, there is a division called the medial
reticular formation. The medial RF is large and has long ascending and
descending fibers, and is surrounded by the lateral reticular
formation. The lateral RF is close to the motor nuclei of the cranial
nerves, and mostly mediates their function.
Medial and lateral reticular formation {{Anchor|Medial and lateral reticular fo
rmation}}
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The medial reticular formation and lateral reticular formation are two
columns of nuclei with ill-defined boundaries that send projections
through the medulla and into the midbrain. The nuclei can be
differentiated by function, cell type, and projections of efferent or
afferent nerves. Moving caudally from the rostral midbrain, at the
site of the rostral pons and the midbrain, the medial RF becomes less
prominent, and the lateral RF becomes more prominent.
Existing on the sides of the medial reticular formation is its lateral
cousin, which is particularly pronounced in the rostral medulla and
caudal pons. Out from this area spring the cranial nerves, including
the very important vagus nerve. The lateral RF is known for its
ganglions and areas of interneurons around the cranial nerves, which
serve to mediate their characteristic reflexes and functions.
Function
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The reticular formation consists of more than 100 small neural
networks, with varied functions including the following:
# Somatic motor control - Some motor neurons send their axons to the
reticular formation nuclei, giving rise to the reticulospinal tracts
of the spinal cord. These tracts function in maintaining tone,
balance, and posture�especially during body movements. The reticular
formation also relays eye and ear signals to the cerebellum so that
the cerebellum can integrate visual, auditory, and vestibular stimuli
in motor coordination. Other motor nuclei include gaze centers, which
enable the eyes to track and fixate objects, and central pattern
generators, which produce rhythmic signals of breathing and
swallowing.
# Cardiovascular control - The reticular formation includes the
cardiac and vasomotor centers of the medulla oblongata.
# Pain modulation - The reticular formation is one means by which pain
signals from the lower body reach the cerebral cortex. It is also the
origin of the descending analgesic pathways. The nerve fibers in these
pathways act in the spinal cord to block the transmission of some pain
signals to the brain.
# Sleep and consciousness - The reticular formation has projections to
the thalamus and cerebral cortex that allow it to exert some control
over which sensory signals reach the cerebrum and come to our
conscious attention. It plays a central role in states of
consciousness like alertness and sleep. Injury to the reticular
formation can result in irreversible coma.
# Habituation - This is a process in which the brain learns to ignore
repetitive, meaningless stimuli while remaining sensitive to others. A
good example of this is a person who can sleep through loud traffic in
a large city, but is awakened promptly due to the sound of an alarm or
crying baby. Reticular formation nuclei that modulate activity of the
cerebral cortex are part of the ascending reticular activating system.
Ascending reticular activating system
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The ascending reticular activating system (ARAS), also known as the
'extrathalamic control modulatory system' or simply the 'reticular
activating system' (RAS), is a set of connected nuclei in the brains
of vertebrates that is responsible for regulating wakefulness and
sleep-wake transitions. The ARAS is a part of the reticular formation
and is mostly composed of various nuclei in the thalamus and a number
of dopaminergic, noradrenergic, serotonergic, histaminergic,
cholinergic, and glutamatergic brain nuclei.
Structure of the ARAS
=======================
The ARAS is composed of several neural circuits connecting the dorsal
part of the posterior midbrain and anterior pons to the cerebral
cortex via distinct pathways that project through the thalamus and
hypothalamus. The ARAS is a collection of different nuclei - more than
20 on each side in the upper brainstem, the pons, medulla, and
posterior hypothalamus. The neurotransmitters that these neurons
release include dopamine, norepinephrine, serotonin, histamine,
acetylcholine, and glutamate. They exert cortical influence through
direct axonal projections and indirect projections through thalamic
relays.
The thalamic pathway consists primarily of cholinergic neurons in the
pontine tegmentum, whereas the hypothalamic pathway is composed
primarily of neurons that release monoamine neurotransmitters, namely
dopamine, norepinephrine, serotonin, and histamine. The
glutamate-releasing neurons in the ARAS were identified much more
recently relative to the monoaminergic and cholinergic nuclei; the
glutamatergic component of the ARAS includes one nucleus in the
hypothalamus and various brainstem nuclei. The orexin neurons of the
lateral hypothalamus innervate every component of the ascending
reticular activating system and coordinate activity within the entire
system.
Key components of the ascending reticular activating system
Nucleus type Corresponding nuclei that mediate arousal Sources
Dopaminergic nuclei *Ventral tegmental area *Substantia nigra pars
compacta
Noradrenergic nuclei *Locus coeruleus *Related noradrenergic
brainstem nuclei
Serotonergic nuclei *Dorsal raphe nucleus *Median raphe nucleus
Histaminergic nuclei *Tuberomammillary nucleus
Cholinergic nuclei *Forebrain cholinergic nuclei *Pontine tegmental
nuclei: laterodorsal and pedunculopontine tegmental nucleus
Glutamatergic nuclei *Brainstem nuclei: parabrachial nucleus,
precoeruleus, and pedunculopontine tegmental nucleus *Hypothalamic
nuclei: supramammillary nucleus
Thalamic nuclei *Thalamic reticular nucleus *Intralaminar nucleus,
including the centromedian nucleus
The ARAS consists of evolutionarily ancient areas of the brain, which
are crucial to the animal's survival and protected during adverse
periods, such as during inhibitory periods of Totsellreflex, aka,
"animal hypnosis".
The ascending reticular activating system which sends neuromodulatory
projections to the cortex - mainly connects to the prefrontal cortex.
There seems to be low connectivity to the motor areas of the cortex.
Neurotransmitters
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The primary neurotransmitters involved in the RAS are dopamine,
norepinephrine, serotonin, histamine, acetylcholine, and glutamate.
Acetylcholine
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Shute and Lewis first revealed the presence of a cholinergic component
of the RAS, composed of two ascending mesopontine tegmental pathways
rostrally situated between the mesencephalon and the centrum
semiovale. These pathways involve cholinergic neurons of the posterior
midbrain, the pedunculopontine nucleus (PPN) and the laterodorsal
tegmental nucleus (LDT), which are active during waking and REM sleep.
Cholinergic activity is highest when in an awake state and during REM
sleep, and is minimal in non-REM sleep Cholinergic activation in the
RAS results in increased acetylcholine release in these areas.
Glutamate has also been suggested to play an important role in
determining the firing patterns of the tegmental cholinergic neurons.
It has been recently reported that significant portions of posterior
PPN cells are electrically coupled. It appears that this process may
help coordinate and enhance rhythmic firing across large populations
of cells. This unifying activity may help facilitate signal
propagation throughout the RAS and promote sleep-wake transitions. It
is estimated that 10 to 15% of RAS cells may be electrically coupled.
Norepinephrine
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The adrenergic component of the reticular activating system is closely
associated with the noradrenergic neurons of the locus coeruleus.
Unlike cholinergic neurons, the adrenergic neurons are active during
waking and slow wave sleep but cease firing during REM sleep. In
addition, adrenergic neurotransmitters are destroyed much more slowly
than acetylcholine. This sustained activity may account for some of
the time latency during changes of consciousness.
More recent work has indicated that the neuronal messenger nitric
oxide (NO) may also play an important role in modulating the activity
of the noradrenergic neurons in the RAS. NO diffusion from dendrites
regulates regional blood flow in the thalamus, where NO concentrations
are high during waking and REM sleep and significantly lower during
slow-wave sleep. Furthermore, injections of NO inhibitors have been
found to affect the sleep-wake cycle and arousal.
Serotonin
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-->
Consciousness
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The ascending reticular activating system is an important enabling
factor for the state of consciousness. The ascending system is seen to
contribute to wakefulness as characterised by cortical and behavioural
arousal.
Regulating sleep-wake transitions
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The main function of the ARAS is to modify and potentiate thalamic and
cortical function such that electroencephalogram (EEG)
desynchronization ensues. There are distinct differences in the
brain's electrical activity during periods of wakefulness and sleep:
Low voltage fast burst brain waves (EEG desynchronization) are
associated with wakefulness and REM sleep (which are
electrophysiologically similar); high voltage slow waves are found
during non-REM sleep. Generally speaking, when thalamic relay neurons
are in burst mode the EEG is synchronized and when they are in tonic
mode it is desynchronized. Stimulation of the ARAS produces EEG
desynchronization by suppressing slow cortical waves (0.3-1 Hz), delta
waves (1-4 Hz), and spindle wave oscillations (11-14 Hz) and by
promoting gamma band (20 - 40 Hz) oscillations.
The physiological change from a state of deep sleep to wakefulness is
reversible and mediated by the ARAS. The ventrolateral preoptic
nucleus (VLPO) of the hypothalamus inhibits the neural circuits
responsible for the awake state, and VLPO activation contributes to
the sleep onset. During sleep, neurons in the ARAS will have a much
lower firing rate; conversely, they will have a higher activity level
during the waking state. In order that the brain may sleep, there must
be a reduction in ascending afferent activity reaching the cortex by
suppression of the ARAS.
Attention
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The ARAS also helps mediate transitions from relaxed wakefulness to
periods of high attention. There is increased regional blood flow
(presumably indicating an increased measure of neuronal activity) in
the midbrain reticular formation (MRF) and thalamic intralaminar
nuclei during tasks requiring increased alertness and attention.
Clinical significance of the ARAS
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Mass lesions in brainstem ARAS nuclei can cause severe alterations in
level of consciousness (e.g., coma). Bilateral damage to the reticular
formation of the midbrain may lead to coma or death.
Direct electrical stimulation of the ARAS produces pain responses in
cats and educes verbal reports of pain in humans. Additionally,
ascending reticular activation in cats can produce mydriasis, which
can result from prolonged pain. These results suggest some
relationship between ARAS circuits and physiological pain pathways.
Pathologies
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Some pathologies of the ARAS may be attributed to age, as there
appears to be a general decline in reactivity of the ARAS with
advancing years. Changes in electrical coupling have been suggested to
account for some changes in ARAS activity: if coupling were
down-regulated, there would be a corresponding decrease in
higher-frequency synchronization (gamma band). Conversely,
up-regulated electrical coupling would increase synchronization of
fast rhythms that could lead to increased arousal and REM sleep drive.
Specifically, disruption of the ARAS has been implicated in the
following disorders:
* Narcolepsy: Lesions along the pedunculopontine (PPT/PPN) /
laterodorsal tegmental (LDT) nuclei are associated with narcolepsy.
There is a significant down-regulation of PPN output and a loss of
orexin peptides, promoting the excessive daytime sleepiness that is
characteristic of this disorder.
* Progressive supranuclear palsy (PSP) : Dysfunction of nitrous oxide
signaling has been implicated in the development of PSP.
* Parkinson's disease: REM sleep disturbances are common in
Parkinson's. It is mainly a dopaminergic disease, but cholinergic
nuclei are depleted as well. Degeneration in the ARAS begins early in
the disease process.
Developmental influences
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There are several potential factors that may adversely influence the
development of the ascending reticular activating system:
* Preterm birth: Regardless of birth weight or weeks of gestation,
premature birth induces persistent deleterious effects on
pre-attentional (arousal and sleep-wake abnormalities), attentional
(reaction time and sensory gating), and cortical mechanisms throughout
development.
* Smoking during pregnancy: Prenatal exposure to cigarette smoke is
known to produce lasting arousal, attentional and cognitive deficits
in humans. This exposure can induce up-regulation of α4β2 nicotinic
receptors on cells of the pedunculopontine nucleus (PPN), resulting in
increased tonic activity, resting membrane potential, and
hyperpolarization-activated cation current. These major disturbances
of the intrinsic membrane properties of PPN neurons result in
increased levels of arousal and sensory gating, deficits (demonstrated
by a diminished amount of habituation to repeated auditory stimuli).
It is hypothesized that these physiological changes may intensify
attentional dysregulation later in life.
Descending reticulospinal tracts
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The reticulospinal tracts, also known as the descending or anterior
reticulospinal tracts, are extrapyramidal motor tracts that descend
from the reticular formation in two tracts to act on the motor neurons
supplying the trunk and proximal limb flexors and extensors. The
reticulospinal tracts are involved mainly in locomotion and postural
control, although they do have other functions as well. The descending
reticulospinal tracts are one of four major cortical pathways to the
spinal cord for musculoskeletal activity. The reticulospinal tracts
works with the other three pathways to give a coordinated control of
movement, including delicate manipulations. The four pathways can be
grouped into two main system pathways - a medial system and a lateral
system. The medial system includes the reticulospinal pathway and the
vestibulospinal pathway, and this system provides control of posture.
The corticospinal and the rubrospinal tract pathways belong to the
lateral system which provides fine control of movement.
Components of the reticulospinal tracts
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The tract is divided into two parts, the medial (or pontine) and
lateral (or medullary) reticulospinal tracts (MRST and LRST).
* The MRST is responsible for exciting anti-gravity, extensor muscles.
The fibers of this tract arise from the caudal pontine reticular
nucleus and the oral pontine reticular nucleus and project to lamina
VII and lamina VIII of the spinal cord.
* The LRST is responsible for inhibiting excitatory axial extensor
muscles of movement. It is also responsible for automatic breathing.
The fibers of this tract arise from the medullary reticular formation,
mostly from the gigantocellular nucleus, and descend the length of the
spinal cord in the anterior part of the lateral column. The tract
terminates in lamina VII mostly with some fibers terminating in lamina
IX of the spinal cord.
The ascending sensory tract conveying information in the opposite
direction is known as the spinoreticular tract.
Functions of the reticulospinal tracts
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#Integrates information from the motor systems to coordinate automatic
movements of locomotion and posture
#Facilitates and inhibits voluntary movement; influences muscle tone
#Mediates autonomic functions
#Modulates pain impulses
#Influences blood flow to lateral geniculate nucleus of the thalamus.
Clinical significance of the reticulospinal tracts
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The reticulospinal tracts provide a pathway by which the hypothalamus
can control sympathetic thoracolumbar outflow and parasympathetic
sacral outflow.
Two major descending systems carrying signals from the brainstem and
cerebellum to the spinal chord can trigger automatic postural response
for balance and orientation: vestibulospinal tracts from the
vestibular nuclei and reticulospinal tracts from the pons and medulla.
Lesions of these tracts result in profound ataxia and postural
instability.
A physical or vascular damage to the brainstem disconnecting the red
nucleus (midbrain) and the vestibular nuclei (pons) may cause
decerebrate rigidity which has the neurological sign of increased
muscle tone and hyperactive stretch reflexes. Responding to a
startling or painful stimulus, both arms and legs extend and turn
internally. The cause is the tonic activity of lateral
vestibulospinal and reticulospinal tracts stimulating extensor
motoneurons without the inhibitions from rubrospinal tract.
A brainstem damage above the red nucleus' level may cause decorticate
rigidity. Responding to a startling or painful stimulus, the arms
flex and the legs extend. The cause is the red nucleus, via the
rubrospinal tract, counteracting the extensor motorneuron's excitation
from the lateral vestibulospinal and reticulospinal tracts. Because
the rubrospinal tract only extends to the cervical spinal chord, it
mostly acts on the arms by exciting the flexor muscles and inhibiting
the extensors, but not on the legs.
A damage to the medulla below the vestibular nuclei may cause flaccid
paralysis, hypotonia, loss of respiratory drive, and quadriplegia.
There are no reflexes resembling early stages of spinal shock because
of complete loss of activities in the motorneurons. The cause is
there is no longer tonic activity from the lateral vestibulospinal and
reticulospinal tracts.
History
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The term "reticular formation" was coined in the late 19th century by
Otto Deiters, coinciding with Ramon y Cajal�s 'neuron doctrine'. Allan
Hobson states in his book 'The Reticular Formation Revisited' that the
name is an etymological vestige from the fallen era of the aggregate
field theory in the neural sciences. The term "reticulum" means
"netlike structure", which is what the reticular formation resembles
at first glance. It has been described as being either too complex to
study or an undifferentiated part of the brain with no organization at
all. Eric Kandel describes the reticular formation as being organized
in a similar manner to the intermediate gray matter of the spinal
cord. This chaotic, loose, and intricate form of organization is what
has turned off many researchers from looking farther into this
particular area of the brain. The cells lack clear ganglionic
boundaries, but do have clear functional organizations and distinct
cell types. The term "reticular formation" is seldom used anymore
except to speak in generalities. Modern scientists usually refer to
the individual nuclei that compose the reticular formation.
Moruzzi and Magoun first investigated the neural components regulating
the brain's sleep-wake mechanisms in 1949. Physiologists had proposed
that some structure deep within the brain controlled mental
wakefulness and alertness. It had been thought that wakefulness
depended only on the direct reception of afferent (sensory) stimuli at
the cerebral cortex.
The direct electrical stimulation of the brain could simulate
electrocortical relays. Magoun used this principle to demonstrate, on
two separate areas of the brainstem of a cat, how to produce
wakefulness from sleep. First the ascending somatic and auditory
paths; second, a series of "ascending relays from the reticular
formation of the lower brain stem through the midbrain tegmentum,
subthalamus and hypothalamus to the internal capsule." The latter was
of particular interest, as this series of relays did not correspond to
any known anatomical pathways for the wakefulness signal transduction
and was coined the 'ascending reticular activating system' (ARAS).
Next, the significance of this newly identified relay system was
evaluated by placing lesions in the medial and lateral portions of the
front of the midbrain. Cats with mesancephalic interruptions to the
ARAS entered into a deep sleep and displayed corresponding brain
waves. In alternative fashion, cats with similarly placed
interruptions to ascending auditory and somatic pathways exhibited
normal sleeping and wakefulness, and could be awakened with somatic
stimuli. Because these external stimuli would be blocked by the
interruptions, this indicated that the ascending transmission must
travel through the newly discovered ARAS.
Finally, Magoun recorded potentials within the medial portion of the
brain stem and discovered that auditory stimuli directly fired
portions of the reticular activating system. Furthermore, single-shock
stimulation of the sciatic nerve also activated the medial reticular
formation, hypothalamus, and thalamus. Excitation of the ARAS did not
depend on further signal propagation through the cerebellar circuits,
as the same results were obtained following decerebellation and
decortication. The researchers proposed that a column of cells
surrounding the midbrain reticular formation received input from all
the ascending tracts of the brain stem and relayed these afferents to
the cortex and therefore regulated wakefulness.
See also
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* Locus coeruleus
* Pedunculopontine nucleus
* Medial pontine reticular formation
* Midbrain reticular formation
Other references
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;Systems of The Body (2010)
*
*
; Neuroscience (2018)
*
; Anatomy and Physiology (2018)
*
*
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Original Article:
http://en.wikipedia.org/wiki/Reticular_formation
