View source for Locus ceruleus

{{BioPsy}}
{{Expert}}



{{Infobox Brain|
  Name            = Locus coeruleus |
  Latin           = locus caeruleus   |
  GraySubject     = 187 |
  GrayPage        = 778 |
  Image           = Gray709.png |
  Caption         = Rhomboid fossa. (Locus coeruleus not labeled, but region is very near colliculus facialis, which is labeled at center left.) |
  Image2          = |
  Caption2        = |
  IsPartOf        = |
  Components      = |
  Artery          = |
  Vein            = |
  Acronym         = |
  BrainInfoType   = hier |
  BrainInfoNumber = 578 |
  MeshName        = |
  MeshNumber      = |
  DorlandsPre     = l_14 |
  DorlandsSuf     = 12501661  |
}}
The '''locus ceruleus''' also spelt '''locus coeruleus''', '''locus caeruleus''', is a nucleus in the [[brain stem]] involved with [[physiology|physiological]] responses to [[stress (medicine)|stress]] and [[panic]]. It was discovered in the 1700s by [[Félix Vicq-d'Azyr]].

Its name is derived from the Latin words "caeruleus" and "locus" meaning, literally, "the blue spot" due to its somewhat azure appearance in unstained brain  tissue. ''Caeruleus'' is the classical Latin spelling, but ''coeruleus'', a more archaic form, is the more common spelling. The spelling ''ceruleus'', formed by contraction of the diphthongs ae or oe into e, is an [[American and British English spelling differences#Simplification of ae .28.C3.A6.29 and oe .28.C5.93.29|American English]] form.

==Anatomy==
The locus coeruleus (or "LC") is located within the dorsal wall of the rostral [[pons]] in the lateral floor of the [[fourth ventricle]]. This nucleus is the principal site for synthesis of [[norepinephrine]] in the brain, and is composed of mostly medium-size neurons. [[Melanin]] granules inside the LC contribute to its blue color; it is thereby also known as the nucleus pigmentosus pontis, meaning "heavily pigmented nucleus of the pons." The [[neuromelanin]] is formed by the [[polymerization]] of norepinephrine and is analogous to the black [[dopamine]]-based neuromelanin in the [[substantia nigra]].

==Connections==
The projections of this nucleus reach far and wide, innervating the spinal cord, the brain stem, [[cerebellum]], hypothalamus, the thalamic relay nuclei, the amygdala, the basal telencephalon, and the cortex. 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. It has been said that a single noradrenergic neuron can innervate the entire cerebral cortex via its branches. 

As an important [[homeostasis|homeostatic]] control center of the body, the locus coeruleus receives [[afferents]] from the [[hypothalamus]]. The [[cingulate gyrus]] and the [[amygdala]] also innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses. The cerebellum and afferents from the [[raphe nuclei]] also project to the LC, particularly the raphe pontis and raphe dorsalis.

The locus coeruleus receives inputs from a number of other brain regions, primarily:
* [[Medial]] [[prefrontal cortex]], whose connection is constant, excitatory, and increases in strength with raised activity levels in the subject
* [[Nucleus paragigantocellularis]], which integrates [[autonomic]] and [[natural environment|environment]]al stimuli
* [[Nucleus prepositus hypoglossi]], which is involved in gaze
* Lateral [[hypothalamus]], which releases [[orexin]], which, as well as its other functions, is excitatory in the locus coeruleus.

==Function==
The locus coeruleus is studied in relation to [[clinical depression]], [[panic disorder]], and [[anxiety]]. Some antidepressant medications including [[reboxetine]], [[venlafaxine]], and [[bupropion]], as well as [[ADHD]] medication [[atomoxetine]], are believed to act on [[neuron]]s in this area. This area of the brain is also intimately involved in [[REM sleep]].

Psychiatric research has documented that enhanced noradrenergic postsynaptic responsiveness in the neuronal pathway (brain circuit) that originates in the locus coeruleus and end in the basolateral nucleus of the [[amygdala]] is a major factor in the pathophysiology of most [[Stress (medicine)|stress]]-induced fear-circuitry disorders and especially in [[posttraumatic stress disorder]] (PTSD). The LC neurons are probably the origin of the first or second “leg” of what has been recently termed the "PTSD candidate circuit." Combat-related PTSD (in a 2005 study of deceased American army veterans from World War II) was shown to be associated with a postmortem diminished number of neurons in the locus coeruleus (LC) on the right side of the brain.<ref>{{cite journal |author=Bracha HS, Garcia-Rill E, Mrak RE, Skinner R |title=Postmortem locus coeruleus neuron count in three American veterans with probable or possible war-related PTSD |journal=The Journal of neuropsychiatry and clinical neurosciences |volume=17 |issue=4 |pages=503–9 |year=2005 |pmid=16387990 |doi=10.1176/appi.neuropsych.17.4.503}}</ref> The role of the LC in PTSD may explain the dramatic effectiveness of two generic medications, [[propranolol]] and [[prazosin]] for the secondary prevention and treatment of PTSD, respectively.{{Fact|date=February 2007}}

===In stress===
The locus coeruleus is responsible for mediating many of the sympathetic effects during [[Stress (medicine)|stress]].  The locus coeruleus is activated by stress, and will respond by increasing [[norepinephrine]] secretion, which in turn will increase cognitive function (through the [[prefrontal cortex]]), increase motivation (through [[nucleus accumbens]]), activate the [[hypothalamic-pituitary-adrenal axis]], and increase the sympathetic discharge/inhibit parasympathetic tone (through the [[brainstem]]).  Specific to the activation of the hypothalamo-pituitary adrenal axis, norepinephrine will stimulate the secretion of [[corticotropin-releasing factor]] from the [[hypothalamus]], which induces [[adrenocorticotropic hormone]] release from the [[anterior pituitary]] and subsequent cortisol synthesis in the [[adrenal glands]].  Norepinephrine released from locus coeruleus will feedback to inhibit its production, and corticotropin-releasing hormone will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.{{Fact|date=March 2009}}

===In opiate withdrawal===
Opioids 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 alpha2 adrenoceptor agonist clonidine is used to counteract this withdrawal effect by decreasing adrenergic neurotransmission from the locus coeruleus.{{Fact|date=March 2009}}

==See also==
* [[Raphe nucleus]]
* [[Substantia nigra]]
* [[Reticular formation]]

==References==
<references/>

==External links==
*[http://faculty.etsu.edu/currie/ras.htm "A Lecture, Higher Brain Function: Activation of the Brain and Levels of Consciousness"] at [[East Tennessee State University]]
* {{BrainMaps|locus%20coeruleus|locus coeruleus}}
* [http://homepage.psy.utexas.edu/homepage/class/Psy301/Salinas/sec2/Brain/31.GIF Diagram] at [[University of Texas at Austin]]
* [http://www.healthsystem.virginia.edu/internet/pediatrics/hcp/adhdbrainanatomy.cfm Diagram] at [[University of Virginia]]
* http://www2.umdnj.edu/~neuro/studyaid/Practical2000/Q45.htm

{{Rhombencephalon}}

[[Category:Brainstem]]
[[Category:Neuroanatomy]]
[[Category:Pons]]

<!--
[[de:Locus caeruleus]]
[[es:Locus coeruleus]]
[[fr:Locus cœruleus]]
[[nl:Locus coeruleus]]
[[ja:青斑核]]
[[pl:Miejsce sinawe]]
[[pt:Cerúleo]]
[[ru:Голубое пятно]]
[[fi:Locus caeruleus]]
[[zh:蓝斑核]]
-->
{{enWP|Locus coeruleus}}