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|Brain: Locus coeruleus|
|Rhomboid fossa. (Locus coeruleus not labeled, but region is very near colliculus facialis, which is labeled at center left.)|
|Gray's||subject #187 778|
The locus ceruleus also spelt locus coeruleus, 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 diphthongs ae or oe into e, is an American English form.
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.
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.
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. 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.[How to reference and link to summary or text]
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.[How to reference and link to summary or text]
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.[How to reference and link to summary or text]
- 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.
- "A Lecture, Higher Brain Function: Activation of the Brain and Levels of Consciousness" at East Tennessee State University
- BrainMaps at UCDavis locus%20coeruleus
- Diagram at University of Texas at Austin
- Diagram at University of Virginia
Brain: rhombencephalon (hindbrain)
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