The reticular formation is a set of interconnected
nuclei that are located throughout the
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
. It is not anatomically well defined, because it includes
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s located in different parts of the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
. 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
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
to the lower part of the
medulla oblongata
The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...
.
The reticular formation includes ascending pathways to the
cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
in the ascending reticular activating system (ARAS) and descending pathways to the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
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
Arousal is the physiological and psychological state of being awoken or of sense organs stimulated to a point of perception. It involves activation of the ascending reticular activating system (ARAS) in the brain, which mediates wakefulness, th ...
and
consciousness
Consciousness, at its simplest, is sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...
. 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
The gigantocellular reticular nucleus (Gi) is a subregion of the medullary reticular formation. As the name indicates, it consists mainly of so-called giant neuronal cells.
This nucleus has been known to innervate the caudal hypoglossal nucleus, ...
(medial zone), and
parvocellular reticular nuclei (lateral zone). The raphe nuclei are the place of synthesis of the neurotransmitter
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
, which plays an important role in mood regulation. The gigantocellular nuclei are involved in motor coordination. The parvocellular nuclei regulate
exhalation
Exhalation (or expiration) is the flow of the breath out of an organism. In animals, it is the movement of air from the lungs out of the airways, to the external environment during breathing.
This happens due to elastic properties of the lungs, ...
.
The reticular formation is essential for governing some of the basic functions of higher organisms and is one of the
phylogenetically
In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...
oldest portions of the brain.
Structure
![Lower pons horizontal KB](https://upload.wikimedia.org/wikipedia/commons/d/dc/Lower_pons_horizontal_KB.svg)
The human reticular formation is composed of almost 100
brain nuclei
In neuroanatomy, a nucleus (plural form: nuclei) is a cluster of neurons in the central nervous system, located deep within the cerebral hemispheres and brainstem. The neurons in one nucleus usually have roughly similar connections and functions. ...
and contains many projections into the
forebrain
In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the Anatomical terms of location#Directional terms, rostral (forward-most) portion of the brain. The forebrain (prosencephalon), the midbrain (mesencephalon), and hin ...
,
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
, and
cerebellum
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
, among other regions.
It includes the
reticular nuclei Reticular nucleus may refer to:
* Caudal pontine reticular nucleus
* Gigantocellular reticular nucleus, a nucleus that innervates the caudal hypoglossal nucleus, and responds to glutamateric stimuli.
* Lateral reticular nucleus
* Oral pontine reti ...
,
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
sagittal
The sagittal plane (; also known as the longitudinal plane) is an anatomical plane that divides the body into right and left sections. It is perpendicular to the transverse and coronal planes. The plane may be in the center of the body and divi ...
ly 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
Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...
in the cat brain. In contrast, lesioning of the more caudal portion of the reticular formation produces
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
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
The medial reticular formation and lateral reticular formation are two columns of
nuclei with ill-defined boundaries that send projections through the
medulla
Medulla or Medullary may refer to:
Science
* Medulla oblongata, a part of the brain stem
* Renal medulla, a part of the kidney
* Adrenal medulla, a part of the adrenal gland
* Medulla of ovary, a stroma in the center of the ovary
* Medulla of t ...
and into the
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
. The nuclei can be differentiated by function, cell type, and projections of
efferent or
afferent nerves. Moving caudally from the rostral
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
, at the site of the rostral
pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of Va ...
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
Lateral is a geometric term of location which may refer to:
Healthcare
*Lateral (anatomy), an anatomical direction
*Lateral cricoarytenoid muscle
*Lateral release (surgery), a surgical procedure on the side of a kneecap
Phonetics
*Lateral cons ...
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 vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and right ...
. The lateral RF is known for its
ganglion
A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympatheti ...
s and areas of
interneurons
Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. In ...
around the
cranial nerves
Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...
, which serve to mediate their characteristic reflexes and functions.
Function
The reticular formation consists of more than 100 small neural networks, with varied functions including the following:
# Somatic
motor
An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy.
Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power g ...
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 postureespecially 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
The Vestibular (from pt, vestíbulo, "entrance hall") is a competitive examination and is the primary and widespread entrance system used by Brazilian universities to select the students admitted.
The Vestibular usually takes place from Novem ...
stimuli in motor coordination. Other motor nuclei include gaze centers, which enable the eyes to track and fixate objects, and
central pattern generator
Central pattern generators (CPGs) are self-organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly-coupled patterns of neural activity that drive rhythmic and stereot ...
s, which produce rhythmic signals of breathing and swallowing.
# Cardiovascular control – The reticular formation includes the cardiac and
vasomotor
Vasomotor refers to actions upon a blood vessel which alter its diameter. More specifically, it can refer to vasodilator action and vasoconstrictor action.
Control Sympathetic innervation
Sympathetic nerve fibers travel around the tunica media of ...
centers of the
medulla oblongata
The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...
.
# Pain modulation – The reticular formation is one means by which pain signals from the lower body reach the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
. It is also the origin of the
descending analgesic pathways
The discography of the experimental music group Psychic TV consists of over 100 full-length albums, over 15 compilation albums and over 30 singles and EPs.
Studio albums
*'' Force the Hand of Chance'' (LP, cassette) (1982)
*'' Themes'' (LP) (19 ...
. 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
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
and cerebral cortex that allow it to exert some control over which sensory signals reach the
cerebrum
The cerebrum, telencephalon or endbrain is the largest part of the brain containing the cerebral cortex (of the two cerebral hemispheres), as well as several subcortical structures, including the hippocampus, basal ganglia, and olfactory bulb. In ...
and come to our conscious
attention
Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Atte ...
. It plays a central role in states of consciousness like
alertness
Alertness is the state of active attention by high sensory awareness such as being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related for psychology . A lack of alertness is a symptom of a ...
and
sleep
Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...
. Injury to the reticular formation can result in irreversible
coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
.
#
Habituation
Habituation is a form of non-associative learning in which an innate (non-reinforced) response to a stimulus decreases after repeated or prolonged presentations of that stimulus. Responses that habituate include those that involve the intact org ...
– 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.
Major subsystems
Ascending reticular activating system
![Gray690](https://upload.wikimedia.org/wikipedia/commons/2/22/Gray690.png)
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
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
s of vertebrates that is responsible for regulating
wakefulness
Wakefulness is a daily recurring Human brain, brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world.
Being awake is the opposite of ...
and
sleep-wake transitions. The ARAS is a part of the reticular formation and is mostly composed of various nuclei in the
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
and a number of
dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...
,
noradrenergic
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
,
serotonergic
Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
,
histaminergic
Histaminergic means "working on the histamine system", and histaminic means "related to histamine".
A histaminergic agent (or drug) is a chemical which functions to directly modulate the histamine system in the body or brain. Examples include his ...
,
cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...
, and
glutamatergic
Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/ aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...
brain nuclei.
Structure of the ARAS
The ARAS is composed of several
neural circuit
A neural circuit is a population of neurons interconnected by synapses to carry out a specific function when activated. Neural circuits interconnect to one another to form large scale brain networks.
Biological neural networks have inspired the ...
s connecting the dorsal part of the posterior
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
and anterior
pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of Va ...
to the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
via distinct pathways that project through the
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
and
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
.
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
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
,
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
,
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
,
histamine
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...
,
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
, and
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
.
They exert cortical influence through direct axonal projections and indirect projections through thalamic relays.
The thalamic pathway consists primarily of
cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...
neurons in the
pontine tegmentum
Pontine may refer to:
* Having to do with the pons, a structure located in the brain stem (from ''pons'', "bridge")
* Pontine Marshes, a region of Italy near Rome
* Pontine Islands
The Pontine Islands (, also ; it, Isole Ponziane ) are an ar ...
, whereas the hypothalamic pathway is composed primarily of neurons that release
monoamine neurotransmitter
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromaticity, aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.
All mo ...
s, 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
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), ...
neurons of the
lateral hypothalamus
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognit ...
innervate every component of the ascending reticular activating system and coordinate activity within the entire system.
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
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...
.
There seems to be low connectivity to the
motor areas of the cortex.
Functions of the ARAS
=Consciousness
=
The ascending reticular activating system is an important enabling factor for the state of
consciousness
Consciousness, at its simplest, is sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...
.
The ascending system is seen to contribute to wakefulness as characterised by cortical and behavioural arousal.
= Regulating sleep-wake transitions
=
The main function of the ARAS is to modify and potentiate thalamic and cortical function such that
electroencephalogram
Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
(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
Neural oscillations, or brainwaves, are rhythmic or repetitive patterns of neural activity in the central nervous system. Neural tissue can generate oscillation, oscillatory activity in many ways, driven either by mechanisms within individual ne ...
(EEG desynchronization) are associated with wakefulness and
REM sleep
Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the sleeper to dream viv ...
(which are electrophysiologically similar); high voltage slow waves are found during non-REM sleep. Generally speaking, when thalamic relay neurons are in
burst
Burst may refer to:
*Burst mode (disambiguation), a mode of operation where events occur in rapid succession
**Burst transmission, a term in telecommunications
**Burst switching, a feature of some packet-switched networks
** Bursting, a signaling m ...
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 wave
Delta waves are high amplitude neural oscillations with a frequency between 0.5 and 4 hertz. Delta waves, like other brain waves, can be recorded with electroencephalography (EEG) and are usually associated with the deep stage 3 of NREM sleep, ...
s (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
The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain ...
(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
=
The ARAS also helps mediate transitions from relaxed wakefulness to periods of high attention
Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Atte ...
. 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
Mass lesions in brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
ARAS nuclei can cause severe alterations in level of consciousness
An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment.
A mildly depressed level of consciousne ...
(e.g., coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
). Bilateral damage to the reticular formation of the midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
may lead to coma or death.
Direct electrical stimulation of the ARAS produces pain responses in cats and elicits verbal reports of pain in humans. Ascending reticular activation in cats can produce mydriasis
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs.
Normally, as ...
, which can result from prolonged pain. These results suggest some relationship between ARAS circuits and physiological pain pathways.
= Pathologies
=
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
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
: Lesions along the pedunculopontine
The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus (PPT or PPTg) is a collection of neurons located in the upper pons in the brainstem. It lies caudal to the substantia nigra and adjacent to the superior cerebellar pedunc ...
(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
Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...
(PSP) : Dysfunction of nitrous oxide
Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has a ...
signaling has been implicated in the development of PSP.
* Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
: 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
There are several potential factors that may adversely influence the development of the ascending reticular activating system:
* Preterm birth
Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 we ...
: 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
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...
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
The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus (PPT or PPTg) is a collection of neurons located in the upper pons in the brainstem. It lies caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. ...
(PPN), resulting in increased tonic activity, resting membrane potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage.
The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as oppo ...
, 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 Sensory gating describes neural processes of filtering out redundant or irrelevant stimuli from all possible environmental stimuli reaching the brain. Also referred to as gating or filtering, sensory gating prevents an overload of information in the ...
, 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
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
The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''co ...
and the rubrospinal tract
The rubrospinal tract is a part of the nervous system. It is a part of the lateral indirect extra-pyramidal tract.
Structure
In the midbrain, it originates in the magnocellular red nucleus, crosses to the other side of the midbrain, and desce ...
pathways belong to the lateral system which provides fine control of movement.
Components of the reticulospinal tracts
This descending 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
The caudal pontine reticular nucleus or nucleus reticularis pontis caudalis is a portion of the reticular formation, composed of gigantocellular neurons.
In rabbits and cats it is exclusively giant cells, however in humans there are normally size ...
and the oral pontine reticular nucleus
The oral pontine reticular nucleus, or rostral pontine reticular nucleus, is delineated from the caudal pontine reticular nucleus. This nucleus tapers into the lower mesencephalic reticular formation and contains sporadic giant cells.
Different po ...
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
The gigantocellular reticular nucleus (Gi) is a subregion of the medullary reticular formation. As the name indicates, it consists mainly of so-called giant neuronal cells.
This nucleus has been known to innervate the caudal hypoglossal 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
The spinoreticular tract is an ascending pathway in the white matter of the spinal cord, positioned closely to the lateral spinothalamic tract. The tract is from spinal cord—to reticular formation— to thalamus.
It is responsible for automati ...
.
Functions of the reticulospinal tracts
#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
In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral projec ...
of the thalamus.
Clinical significance of the reticulospinal tracts
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 cord can trigger automatic postural response for balance
Balance or balancing may refer to:
Common meanings
* Balance (ability) in biomechanics
* Balance (accounting)
* Balance or weighing scale
* Balance as in equality or equilibrium
Arts and entertainment Film
* ''Balance'' (1983 film), a Bulgaria ...
and orientation: vestibulospinal tracts The vestibulospinal tract is a neural tract in the central nervous system. Specifically, it is a component of the extrapyramidal system and is classified as a component of the medial pathway. Like other descending motor pathways, the vestibulospinal ...
from the vestibular nuclei
The vestibular nuclei (VN) are the cranial nuclei for the vestibular nerve located in the brainstem.
In Terminologia Anatomica they are grouped in both the pons and the medulla in the brainstem.
Structure Path
The fibers of the vestibular nerve ...
and reticulospinal tracts from the pons and medulla. Lesions
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals.
Types
There is no designated classifi ...
of these tracts result in profound ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
and postural instability
A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness, or wooziness, or having a sensation of movement, spinning, or floating. Equilibr ...
.
Physical or vascular damage to the brainstem disconnecting the red nucleus
The red nucleus or nucleus ruber is a structure in the rostral midbrain involved in motor coordination. The red nucleus is pale pink, which is believed to be due to the presence of iron in at least two different forms: hemoglobin and ferritin. ...
(midbrain) and the vestibular nuclei
The vestibular nuclei (VN) are the cranial nuclei for the vestibular nerve located in the brainstem.
In Terminologia Anatomica they are grouped in both the pons and the medulla in the brainstem.
Structure Path
The fibers of the vestibular nerve ...
(pons) may cause decerebrate rigidity, which has the neurological sign of increased muscle tone
In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial muscle contraction, contraction of the muscles, or the muscle's resistance to passive stretch during resting state.O’Sull ...
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
The rubrospinal tract is a part of the nervous system. It is a part of the lateral indirect extra-pyramidal tract.
Structure
In the midbrain, it originates in the magnocellular red nucleus, crosses to the other side of the midbrain, and desce ...
.
Brainstem damage above the red nucleus level may cause decorticate rigidity
Abnormal posturing is an involuntary flexion or Extension (kinesiology), extension of the arms and legs, indicating severe Acquired brain injury, brain injury. It occurs when one set of muscles becomes incapacitated while the opposing set is n ...
. 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 cord, it mostly acts on the arms by exciting the flexor muscles and inhibiting the extensors, rather than the legs.
Damage to the medulla below the vestibular nuclei may cause flaccid paralysis
Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma). This abnormal condition may be caused by disease or by trauma affecting the nerves associated ...
, hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...
, loss of respiratory drive
The control of ventilation refers to the physiological mechanisms involved in the control of breathing, which is the movement of air into and out of the lungs. Ventilation facilitates respiration. Respiration refers to the utilization of oxygen a ...
, and quadriplegia. There are no reflexes resembling early stages of spinal shock Spinal shock was first explored by Whytt in 1750 as a loss of sensation accompanied by motor paralysis with initial loss but gradual recovery of reflexes, following a spinal cord injury (SCI) – most often a complete transection. Reflexes in the sp ...
because of complete loss of activity in the motorneurons, as there is no longer any tonic activity arising from the lateral vestibulospinal and reticulospinal tracts.
History
The term "reticular formation" was coined in the late 19th century by Otto Deiters
Otto Friedrich Karl Deiters (; 15 November 1834 – 5 December 1863) was a German neuroanatomist. He was born in Bonn, studied at the University of Bonn, and spent most of his professional career in Bonn. He is remembered for his microscopic ...
, coinciding with Ramon y Cajal's ''neuron doctrine
The neuron doctrine is the concept that the nervous system is made up of discrete individual cells, a discovery due to decisive neuro-anatomical work of Santiago Ramón y Cajal and later presented by, among others, H. Waldeyer-Hartz. The term ''n ...
''. Allan Hobson
John Allan Hobson (June 3, 1933 – July 7, 2021) was an American psychiatrist and dream researcher. He was known for his research on rapid eye movement sleep. He was Professor of Psychiatry, Emeritus, Harvard Medical School, and Professor, Depar ...
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
Reticulum is a small, faint constellation in the southern sky. Its name is Latin for a small net, or reticle—a net of crosshairs at the focus of a telescope eyepiece that is used to measure star positions. The constellation is best viewed b ...
" 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
Eric Richard Kandel (; born Erich Richard Kandel, November 7, 1929) is an Austrian-born American medical doctor who specialized in psychiatry, a neuroscientist and a professor of biochemistry and biophysics at the College of Physicians and Surge ...
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 ganglion
A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympatheti ...
ic boundaries, but do have clear functional organization 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 cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
.
As 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. He first stimulated the ascending somatic
Somatic may refer to:
* Somatic (biology), referring to the cells of the body in contrast to the germ line cells
** Somatic cell, a non-gametic cell in a multicellular organism
* Somatic nervous system, the portion of the vertebrate nervous sys ...
and auditory paths; second, a series of "ascending relays from the reticular formation of the lower brain stem through the midbrain tegmentum
The midbrain is anatomically delineated into the tectum (roof) and the tegmentum (floor). The midbrain tegmentum extends from the substantia nigra to the cerebral aqueduct in a horizontal section of the midbrain. It forms the floor of the midbrain ...
, subthalamus
The subthalamus or prethalamus is a part of the diencephalon. Its most prominent structure is the subthalamic nucleus. The subthalamus connects to the globus pallidus, a basal nucleus of the telencephalon.
Structure
The subthalamus is locate ...
and hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
to the internal capsule
The internal capsule is a white matter structure situated in the inferomedial part of each cerebral hemisphere of the brain. It carries information past the basal ganglia, separating the caudate nucleus and the thalamus from the putamen and the g ...
." 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
Lateral is a geometric term of location which may refer to:
Healthcare
*Lateral (anatomy), an anatomical direction
*Lateral cricoarytenoid muscle
*Lateral release (surgery), a surgical procedure on the side of a kneecap
Phonetics
*Lateral cons ...
portions of the front of the midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
. Cats with mesencephalic 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 physical stimuli. Because these external stimuli would be blocked on their way to the cortex 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
The sciatic nerve, also called the ischiadic nerve, is a large nerve in humans and other vertebrate animals which is the largest branch of the sacral plexus and runs alongside the hip joint and down the lower limb. It is the longest and widest si ...
also activated the medial reticular formation, hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
, and thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
. 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
* Locus coeruleus
The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system.
The locus coerule ...
* Pedunculopontine nucleus
The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus (PPT or PPTg) is a collection of neurons located in the upper pons in the brainstem. It lies caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. ...
* Medial pontine reticular formation The medial pontine reticular formation (MPRF) is a part of the human brain located in the pons of the brainstem (specifically the central pontine reticular formation). It plays a critical function in the generation of REM sleep.
Role in REM sleep
...
* Midbrain reticular formation
The midbrain reticular formation (MRF), also known as reticular formation of midbrain, mesencephalic reticular formation, tegmental reticular formation, and formatio reticularis (tegmenti) mesencephali, is a structure in the midbrain consisting of ...
Footnotes
References
Other references
;Systems of The Body (2010)
*
*
; Neuroscience (2018)
*
; Anatomy and Physiology (2018)
*
*
External links
*
{{Authority control
Brainstem
Neuroscience of sleep