The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a
nucleus in the
pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other mammals, 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 ...
of 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 conti ...
involved with
physiological
Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
responses to
stress and
panic. It is a part of the
reticular activating system
The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks ...
in the
reticular formation
The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks ...
.
The locus coeruleus, which in Latin means "blue spot", is the principal site for brain synthesis of
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
(noradrenaline). The locus coeruleus and the areas of the body affected by the norepinephrine it produces are described collectively as the locus coeruleus-noradrenergic system or LC-NA system.
[
] Norepinephrine may also be released directly into the blood from the
adrenal medulla.
Anatomy

The locus coeruleus (LC) is located in the posterior area of the rostral
pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other mammals, 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 ...
in the lateral floor of the
fourth ventricle. It is composed of mostly medium-size
neurons
A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
.
Melanin
Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes.
There are ...
granules inside the neurons contribute to its blue colour. Thus, it is also known as the ''blue nucleus'', or the ''nucleus pigmentosus pontis'' (heavily pigmented pontine nucleus).
The
neuromelanin is formed by the
polymerization
In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...
of norepinephrine and is analogous to the black
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
-based neuromelanin in the
substantia nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...
.
In adult humans (19-78) the locus coeruleus has 22,000 to 51,000 total pigmented neurons that range in size between 31,000 and 60,000 μm
3.
Connections
The projections of this nucleus reach far and wide. For example, they innervate the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
, the brain stem,
cerebellum
The cerebellum (: cerebella or cerebellums; 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 it or eve ...
,
hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
, the
hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
,
the thalamic relay nuclei, the
amygdala
The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...
, the basal
telencephalon
The cerebrum (: cerebra), 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 olf ...
, and 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 ...
. The norepinephrine from the LC has an excitatory effect on most of the brain, mediating
arousal and priming the brain's neurons to be activated by stimuli.
As an important
homeostatic control center of the body, the locus coeruleus receives
afferents from the hypothalamus. The
cingulate gyrus
The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cin ...
and the amygdala also innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses. The cerebellum and afferents from the
raphe nuclei
The raphe nuclei (, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the ...
also project to the LC, in particular the
pontine raphe nucleus and
dorsal raphe nucleus
The dorsal raphe nucleus is one of the raphe nuclei. It is situated in the brainstem at the midline. It has rostral and caudal subdivisions:
* The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolater ...
.
Inputs
The locus coeruleus receives inputs from a number of other brain regions, primarily:
*The
Medial prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...
, whose connection is constant, excitatory, and increases in strength with raised activity levels in the subject
*The
Nucleus paragigantocellularis, which integrates
autonomic and
environmental stimuli
*The
Nucleus prepositus, which is involved in gaze
*The Lateral hypothalamus, which releases
orexin, which, as well as its other functions, is excitatory in the locus coeruleus.
Outputs
The projections from the locus coeruleus consist of neurons that utilize norepinephrine as their primary neurotransmitter.
These projections include the following connections:
:* LC →
Amygdala
The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...
and
Hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
:* LC →
Brain stem
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 co ...
and
Spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
:* LC →
Cerebellum
The cerebellum (: cerebella or cerebellums; 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 it or eve ...
:* LC →
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. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
:* LC →
Hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
:* LC →
Tectum
The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum.
It is functionally associated with vision, hearing, mo ...
:* LC →
Thalamus
The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...
:* LC →
Ventral tegmental area
The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...
Function
It is related to many functions via its widespread projections. The LC-NA system modulates cortical, subcortical, cerebellar, brainstem, and spinal cord circuits. Some of the most important functions influenced by this system are:
*
Arousal and
sleep-wake cycle
*
Attention
Attention or focus, is the concentration of awareness on some phenomenon to the exclusion of other stimuli. It is the selective concentration on discrete information, either subjectively or objectively. William James (1890) wrote that "Atte ...
and
memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...
* Behavioral and
cognitive flexibility,
creativity
Creativity is the ability to form novel and valuable Idea, ideas or works using one's imagination. Products of creativity may be intangible (e.g. an idea, scientific theory, Literature, literary work, musical composition, or joke), or a physica ...
, behavioral inhibition and
stress (psychological)
*
Cognitive control
*
Decision making
In psychology, decision-making (also spelled decision making and decisionmaking) is regarded as the cognitive process resulting in the selection of a belief or a course of action among several possible alternative options. It could be either ra ...
and utility maximization
*
Emotions
Emotions are physical and mental states brought on by neurophysiology, neurophysiological changes, variously associated with thoughts, feelings, behavior, behavioral responses, and a degree of pleasure or suffering, displeasure. There is ...
*
Neuroplasticity
Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through neurogenesis, growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewir ...
* Posture and
balance
Balance may refer to:
Common meanings
* Balance (ability) in biomechanics
* Balance (accounting)
* Balance or weighing scale
* Balance, as in equality (mathematics) or equilibrium
Arts and entertainment Film
* Balance (1983 film), ''Balance'' ( ...
* Global model failure where predictions about the world are strongly violated
The locus coeruleus is a part of the
reticular activating system
The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks ...
, and is almost completely inactivated in
rapid eye movement sleep
Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals (including humans) and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the s ...
.
Pathophysiology
The locus coeruleus may figure in
clinical depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
,
panic disorder
Panic disorder is a mental disorder, specifically an anxiety disorder, characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
,
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
and
anxiety
Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
. Some medications including
norepinephrine reuptake inhibitors (
reboxetine,
atomoxetine
Atomoxetine, formerly sold under the brand name Strattera, is a selective norepinephrine reuptake inhibitor (sNRI) medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndr ...
),
serotonin-norepinephrine reuptake inhibitors (
venlafaxine,
duloxetine), and
norepinephrine-dopamine reuptake inhibitors (
bupropion) are believed to show efficacy by acting upon
neuron
A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
s in this area.
Research continues to reveal that
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
(NE) is a critical regulator of numerous activities from stress response, the formation of memory to attention and arousal. Many neuropsychiatric disorders precipitate from alterations to NE modulated neurocircuitry: disorders of affect, anxiety disorders, PTSD, ADHD and Alzheimer's disease. Alterations in the locus coeruleus (LC) accompany dysregulation of NE function and likely play a key role in the pathophysiology of these neuropsychiatric disorders.
In stress
The locus coeruleus is responsible for mediating many of the sympathetic effects during stress. The locus coeruleus is activated by stress, and will respond by increasing norepinephrine secretion, which in turn will alter cognitive function (through the prefrontal cortex), increase motivation (through
nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
), activate the
hypothalamic-pituitary-adrenal axis, and increase the sympathetic
discharge/inhibit parasympathetic tone (through 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 conti ...
). Specific to the activation of the hypothalamic-pituitary adrenal axis, norepinephrine will stimulate the secretion of
corticotropin-releasing factor from the hypothalamus, that induces
adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...
release from the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
and subsequent cortisol synthesis in the
adrenal glands. Norepinephrine released from locus coeruleus will feedback to inhibit its production, and corticotropin-releasing factor will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.
The LC's role in cognitive function in relation to stress is complex and multi-modal. Norepinephrine released from the LC can act on α2 receptors to increase working memory, or an excess of NE may decrease working memory by binding to the lower-affinity α1 receptors.
Psychiatric research has documented that enhanced noradrenergic postsynaptic responsiveness in the neuronal pathway (brain circuit) that originates in the locus coeruleus and ends in the
basolateral nuclear complex of the
amygdala
The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...
is a major factor in the pathophysiology of most stress-induced fear-circuitry disorders and especially in
posttraumatic stress disorder
Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...
(PTSD). The LC neurons are probably the origin of the first or second "leg" of the "PTSD circuit." An important 2005 study of deceased American army veterans from World War II has shown combat-related PTSD to be associated with a postmortem-diminished number of neurons in the locus coeruleus on the right side of the brain.
In opiate withdrawal
Opioid
Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s inhibit the firing of neurons in the locus coeruleus. When opioid consumption is stopped, the increased activity of the locus coeruleus contributes to the symptoms of opiate withdrawal. The
α2 adrenergic receptor agonist
clonidine is used to counteract this withdrawal effect by decreasing adrenergic neurotransmission from the locus coeruleus.
Rett syndrome
The genetic defect of the transcriptional regulator
MECP2 is responsible for
Rett syndrome.
A MECP2 deficiency has been associated to catecholaminergic dysfunctions related to autonomic and sympathoadrenergic system in mouse models of Rett Syndrome (RTT). The locus coeruleus is the major source of noradrenergic innervation in the brain and sends widespread connections to rostral (cerebral cortex, hippocampus, hypothalamus) and caudal (cerebellum, brainstem nuclei) brain areas
[Hokfelt T, Martensson R, Bjorklund A, Kleinau S, Goldstein M. 1984. Distribution maps of tyrosine-hydroxylase-immunoreactive neurons in the rat brain. In Handbook of Chemical Neuroanatomy, Vol. 2. Classical Transmitters in the CNS, Part I ( A. Bjorklund and T. Hokfelt, eds.) pp. 277-379. Elsevier, New York.] and.
Indeed, an alteration of this structure could contribute to several symptoms observed in MECP2-deficient mice. Changes in the electrophysiological properties of cells in the
locus ceruleus were shown. These Locus Coeruleus cell changes include hyperexcitability and decreased functioning of its noradrenergic innervation.
A reduction of the tyrosine hydroxylase (TH) mRNA level, the rate-limiting enzyme in catecholamine synthesis, was detected in the whole pons of MECP2-null male as well as in adult heterozygous female mice. Using immunoquantification techniques, a decrease of TH protein staining level, number of locus coeruleus TH-expressing neurons and density of dendritic arborization surrounding the structure was shown in symptomatic MECP2-deficient mice.
However, locus coeruleus cells are not dying but are more likely losing their fully mature phenotype, since no apoptotic neurons in the pons were detected.
Researchers have concluded that, "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett Syndrome, such as respiration and cognition, we hypothesize that the locus coeruleus is a critical site at which loss of MECP2 results in CNS dysfunction. Restoration of normal locus ceruleus function may therefore be of potential therapeutic value in the treatment of Rett Syndrome."
This could explain why a norepinephrine reuptake inhibitor (
desipramine, DMI), which enhances the extracellular NE levels at all noradrenergic synapses, ameliorated some Rett syndrome symptoms in a mouse model of Rett syndrome.
Neurodegenerative diseases
The locus coeruleus is affected in many forms of neurodegenerative diseases: genetic and idiopathic
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
,
progressive supranuclear palsy,
Pick's disease, and
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
. It is also affected in
Down syndrome.
[Esiri MM. et al. (2004). Neuropathology of dementia. 2nd ed. Cambridge University Press.] For example, there is up to 80% loss of locus coeruleus neurons in
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
,
Mouse models of Alzheimer's disease show accelerated progression after chemical destruction of the locus coeruleus.
Neurofibrillary tangle
Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary Biomarker (medicine), biomarker of Alzheimer's disease. Their presence is also found in numerous other disea ...
s, a primary biomarker of Alzheimer's disease, may be found in the locus coeruleus decades before any clinical symptoms. The norepinephrine from locus coeruleus cells in addition to its neurotransmitter role locally diffuses from "varicosities". As such it provides an endogenous
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...
agent in the microenvironment around the neurons,
glial cell
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...
s, and blood vessels in the neocortex and hippocampus.
It has been shown that norepinephrine stimulates mouse microglia to suppress
Aβ-induced production of
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s and promotes
phagocytosis
Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
of Aβ.
This suggests that degeneration of the locus coeruleus might be responsible for increased Aβ deposition in AD brains.
Degeneration of pigmented neurons in this region in Alzheimer's and Parkinson's disease can be visualized in vivo with Neuromelanin
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
. Since the marked degeneration of locus coeruleus, and the neuroprotective properties of noradrenaline,
Ian Robertson proposed the "''Noradrenergic Theory of Cognitive Reserve''" which postulates that the upregulation of the locus coeruleus-noradrenergic system throughout the lifespan may enhance cognitive stimulation contributing to
cognitive reserve preventing from neurodegeneration. Evidence appear to support this theory reporting the locus coeruleus integrity primarily responsible of biological brain maintenance,
including brain clearance, cognitive efficiency, and reduced neuropathological burden.
Sleep deprivation
Animal studies showed that
sleep deprivation
Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either Chronic (medicine), chronic ...
can reduce the number of neurons in the locus coeruleus. Therefore the possibility of lasting damages to human brain functions due to sleep deprivation has become a matter of discussion.
History
The locus coeruleus was discovered in 1784 by
Félix Vicq-d'Azyr,
redescribed later by
Johann Christian Reil in 1809
and named by the brothers Joseph and Karl Wenzel in 1812.
[Swanson, LW. Neuroanatomical terminology : a lexicon of classical origins and historical foundations. Oxford University Press, 2014. England ] High
monoamine oxidase
Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...
activity in the rodent LC was found in 1959,
monoamines were found in 1964 and the widespread projections of noradrenergic neurons in the 1970s.
An important advance in understanding the anatomical organization of the locus coeruleus was the application of the
Falck-Hillarp technique, which combines freeze-dried tissue and formaldehyde to cause catecholamines (such as norepinephrine) and serotonin to fluoresce in tissue sections.
Etymology
''Coeruleus or caeruleus''
The 'English' name ''locus coeruleus''
[Anderson, D.M. (2000). ''Dorland's illustrated medical dictionary'' (29th edition). Philadelphia/London/Toronto/Montreal/Sydney/Tokyo: W.B. Saunders Company.] is actually a Latin expression consisting of the noun, ''locus'', "place" or "spot"
[Lewis, C.T. & Short, C. (1879). ''A Latin dictionary founded on Andrews' edition of Freund's Latin dictionary.'' Oxford: Clarendon Press.] and the adjective ''coeruleus'', "dark blue"
or "sky-blue".
[Kraus, L.A. (1844). ''Kritisch-etymologisches medicinisches Lexikon'' (Dritte Auflage). Göttingen: Verlag der Deuerlich- und Dieterichschen Buchhandlung.][Foster, F.D. (1891-1893). ''An illustrated medical dictionary. Being a dictionary of the technical terms used by writers on medicine and the collateral sciences, in the Latin, English, French, and German languages.'' New York: D. Appleton and Company.] This was aptly translated into English as ''blue place'' in 1907 in the English translation
[Barker, L.W. (1907). ''Anatomical terminology with special reference to the NA With vocabularies in Latin and English and illustrations.'' Philadelphia: P. Blakiston's Son & Co.] of the official Latin anatomic nomenclature of 1895, ''
Nomina Anatomica''. The name of the ''locus coeruleus'' is derived from its azure appearance in unstained brain tissue.
The color is due to light scattering from
neuromelanin in
noradrenergic (producing norepinephrine) nerve cell bodies.
The spelling ''coeruleus'' is actually considered incorrect,
[Triepel, H. (1910). ''Die anatomischen Namen. Ihre Ableitung und Aussprache. Mit einem Anhang: Biographische Notizen.''(Dritte Auflage). Wiesbaden: Verlag J.F. Bergmann.] with dictionaries of classical Latin preferring ''caeruleus''
[Wageningen, J. van & Muller, F. (1921). ''Latijnsch woordenboek.'' (3de druk).
Groningen/Den Haag: J.B. Wolters' Uitgevers-Maatschappij] instead. ''Caeruleus'' is derived from ''caelum'',
hence the spelling with -ae, like caeluleus → caeruleus.
''Caelum'' in classical Latin could refer to ''the sky'', ''the heaven'' or ''the vault of heaven''.
In
mediaeval Latin, orthographic variants such as ''coelum''
[Niermeyer, J.F. (1976). ''Mediae Latinitatis lexicon minus.Lexique Latin médiéval-Français/Anglais. A medieval Latin-French/English dictionary.'' Leiden: E.J. BriLL.] for classical Latin ''caelum''
and ''cerulans''
for classical Latin ''caerulans''
can be found. In English, the color adjective ''cerulean'' is derived from Latin ''caeruleus''.
[Donald, J. (1880). ''Chambers's etymological dictionary of the English language.'' London/Edinburgh: W. & R. Chambers.] In addition, ''
ceiling'' is ultimately derived from Latin ''caelum''.
[Klein, E. (1971). A comprehensive etymological dictionary of the English language. Dealing with the origin of words and their sense development thus illustration the history of civilization and culture. Amsterdam: Elsevier Science B.V.]
''Official Latin nomenclature''
The official Latin nomenclature, ''
Nomina Anatomica'' as ratified in
Basel
Basel ( ; ), also known as Basle ( ), ; ; ; . is a city in northwestern Switzerland on the river Rhine (at the transition from the High Rhine, High to the Upper Rhine). Basel is Switzerland's List of cities in Switzerland, third-most-populo ...
in 1895
[His, W. (1895). ''Die anatomische Nomenclatur. Nomina Anatomica. Der von der Anatomischen Gesellschaft auf ihrer IX. Versammlung in Basel angenommenen Namen''. Leipzig: Verlag Veit & Comp.] and in
Jena
Jena (; ) is a List of cities and towns in Germany, city in Germany and the second largest city in Thuringia. Together with the nearby cities of Erfurt and Weimar, it forms the central metropolitan area of Thuringia with approximately 500,000 in ...
in 1935
[Kopsch, F. (1941). ''Die Nomina anatomica des Jahres 1895 (B.N.A.) nach der Buchstabenreihe geordnet und gegenübergestellt den Nomina anatomica des Jahres 1935 (I.N.A.)'' (3. Auflage). Leipzig: Georg Thieme Verlag.][Stieve, H. (1949). ''Nomina Anatomica. Zusammengestellt von der im Jahre 1923 gewählten Nomenklatur-Kommission, unter Berücksichtigung der Vorschläge der Mitglieder der Anatomischen Gesellschaft, der Anatomical Society of Great Britain and Ireland, sowie der American Association of Anatomists, überprüft und durch Beschluß der Anatomischen Gesellschaft auf der Tagung in Jena 1935 endgúltig angenommen.'' (4th edition). Jena: Verlag Gustav Fischer.] contained the orthographically correct form ''locus caeruleus''. The ''Nomina Anatomica'' published in 1955
[International Anatomical Nomenclature Committee (1955). ''Nomina Anatomica'' . London/Colchester:Spottiswoode, Ballantyne and Co. Ltd.] inadvertently introduced the incorrect spelling ''locus coeruleus'', without further explanation. The subsequent edition monophthongized the
diphthong
A diphthong ( ), also known as a gliding vowel or a vowel glide, is a combination of two adjacent vowel sounds within the same syllable. Technically, a diphthong is a vowel with two different targets: that is, the tongue (and/or other parts of ...
, resulting in ''locus ceruleus'',
[Donáth, T. & Crawford, G.C.N. (1969). ''Anatomical dictionary with nomenclature and explanatory notes.'' Oxford/London/Edinburgh/New York/Toronto/Sydney/Paris/Braunschweig: Pergamon Press.] as they proclaimed that: "All diphthongs should be eliminated".
[International Anatomical Nomenclature Committee (1966). ''Nomina Anatomica''. Amsterdam: Excerpta Medica Foundation.] This form was retained in the subsequent edition.
The following two editions from 1977
[International Anatomical Nomenclature Committee (1977). ''Nomina Anatomica, together with Nomina Histologica and Nomina Embryologica''. Amsterdam-Oxford: Excerpta Medica.]
and 1983
[International Anatomical Nomenclature Committee (1983). ''Nomina Anatomica, together with Nomina Histologica and Nomina Embryologica''. Baltimore/London: Williams & Wilkins] reverted the orthography back to the incorrect spelling ''locus coeruleus'', while the subsequent edition from 1989
[International Anatomical Nomenclature Committee (1989). ''Nomina Anatomica, together with Nomina Histologica and Nomina Embryologica''. Edinburgh: Churchill Livingstone.] eventually returned to the correct spelling ''locus caeruleus''. The current edition of the ''Nomina Anatomica'', rebaptized as ''
Terminologia Anatomica'',
[Federative Committee on Anatomical Terminology (FCAT) (1998). ''Terminologia Anatomica''. Stuttgart: Thieme] dictates ''locus caeruleus'' in its list of Latin expressions and correspondingly mentions ''locus caeruleus'' in its list of English equivalents. This is in line with the statement made by the chairman of the ''Terminologia Anatomica'' that "the committee decided that Latin terms when used in English should be in correct Latin".
In popular culture
On ''
The Big Bang Theory
''The Big Bang Theory'' is an American television sitcom created by Chuck Lorre and Bill Prady for CBS. It aired from September 24, 2007, to May 16, 2019, running for 12 seasons and 279 episodes.
The show originally centered on five charact ...
'', season 5, episode 16 ("The Vacation Solution"), Amy tasks Sheldon with removing the locus coeruleus from a tissue sample.
In Season 3, Episode 14 of Fear The Walking Dead, a man offers preserved Locus Coeruleus as drugs.
References
External links
"A Lecture, Higher Brain Function: Activation of the Brain and Levels of Consciousness"at
East Tennessee State University
East Tennessee State University (ETSU) is a public research university in Johnson City, Tennessee. It was historically part of the State University and Community College System of Tennessee under the Tennessee Board of Regents, but since 2016, ...
Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer's disease and Parkinson's disease*
Diagramat
University of Texas at Austin
The University of Texas at Austin (UT Austin, UT, or Texas) is a public university, public research university in Austin, Texas, United States. Founded in 1883, it is the flagship institution of the University of Texas System. With 53,082 stud ...
Diagram at
University of Virginia
The University of Virginia (UVA) is a Public university#United States, public research university in Charlottesville, Virginia, United States. It was founded in 1819 by Thomas Jefferson and contains his The Lawn, Academical Village, a World H ...
* https://web.archive.org/web/20070512234228/http://www2.umdnj.edu/~neuro/studyaid/Practical2000/Q45.htm
{{DEFAULTSORT:Locus Coeruleus
Pons
Norepinephrine