Locus Coeruleus
The locus coeruleus (LC) is located in the posterior area of the rostral pons in the lateral floor of the fourth ventricle. It is composed of mostly medium-size neurons. Melanin granules inside the neurons of the LC contribute to its blue colour. Thus, it is 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. 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 μm3.*1
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), activate the hypothalamic-pituitary-adrenal axis, and increase the sympathetic discharge/inhibit parasympathetic tone (through the brainstem). 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 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 factor will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.*2
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.*3
References:
- "Mouton PR, Pakkenberg B, Gundersen HJ, Price DL (August 1994). "Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals". J. Chem. Neuroanat. 7 (3): 185–90. doi:10.1016/0891-0618(94)90028-0. PMID 7848573. S2CID 25412090.
- Benarroch EE (November 2009). "The locus coeruleus norepinephrine system: functional organization and potential clinical significance". Neurology. 73 (20): 1699–704. doi:10.1212/wnl.0b013e3181c2937c. PMID 19917994. S2CID 28805417.
- Ramos BP, Arnsten AF (2007). "Adrenergic pharmacology and cognition: focus on the prefrontal cortex". Pharmacol Ther. 113 (3): 523–536. doi:10.1016/j.pharmthera.2006.11.006. PMC 2151919. PMID 17303246.