Locus coeruleus: Difference between revisions
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===In opiate withdrawal=== |
===In opiate withdrawal=== |
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[[Opioid|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}} |
[[Opioid|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}} |
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===Rett syndrome === |
===Rett syndrome === |
Revision as of 01:04, 12 November 2009
This article needs additional citations for verification. (December 2008) |
Locus coeruleus | |
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![]() Rhomboid fossa. (Locus coeruleus not labeled, but region is very near colliculus facialis, which is labeled at center left.) | |
Details | |
Identifiers | |
Latin | locus caeruleus |
MeSH | D008125 |
NeuroNames | 583 |
NeuroLex ID | birnlex_905 |
TA98 | A14.1.05.436 A14.1.05.706 |
TA2 | 5944 |
FMA | 72478 |
Anatomical terms of neuroanatomy |
The Locus coeruleus, also spelled locus caeruleus, is a nucleus in the brain stem involved with physiological responses to 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 digraph ae or oe into e, is an 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 noradrenaline (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 noradrenaline 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 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 environmental 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 neurons 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-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.[1] 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.[citation needed]
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 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.[citation needed]
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.[citation needed]
Rett syndrome
The loss of MECP2 the genetic defect responsible for Rett syndrome changes the properties of cells in the locus ceruleus the exclusive source of noradrenergic innervation to the cerebral cortex and hippocampus. These locus ceruleus cell changes include hyperexcitability and decreased functioning of its noradrenergic innervation.[2] 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 ceruleus 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."[2]
See also
References
- ^ Bracha HS, Garcia-Rill E, Mrak RE, Skinner R (2005). "Postmortem locus coeruleus neuron count in three American veterans with probable or possible war-related PTSD". The Journal of neuropsychiatry and clinical neurosciences. 17 (4): 503–9. doi:10.1176/appi.neuropsych.17.4.503. PMID 16387990.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Taneja P, Ogier M, Brooks-Harris G, Schmid DA, Katz DM, Nelson SB. (2009). Pathophysiology of Locus Ceruleus Neurons in a Mouse Model of Rett Syndrome. Journal of Neuroscience, 29(39):12187–12195. doi:10.1523/JNEUROSCI.3156-09.2009
External links
- "A Lecture, Higher Brain Function: Activation of the Brain and Levels of Consciousness" at East Tennessee State University
- Stained brain slice images which include the "locus coeruleus" at the BrainMaps project
- Diagram at University of Texas at Austin
- Diagram at University of Virginia
- http://www2.umdnj.edu/~neuro/studyaid/Practical2000/Q45.htm