[3] The locus coeruleus, which in Latin means "blue spot", is the principal site for brain synthesis of norepinephrine (noradrenaline).

The locus coeruleus (LC) is located in the posterior area of the rostral pons in the lateral floor of the fourth ventricle.

For example, they innervate the spinal cord, the brain stem, cerebellum, hypothalamus, the hippocampus, the thalamic relay nuclei, the amygdala, the basal telencephalon, and the cortex.

The cingulate gyrus and the amygdala also innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses.

Research continues to reveal that norepinephrine (NE) is a critical regulator of numerous activities from stress response, the formation of memory to attention and arousal.

Alterations in the locus coeruleus (LC) accompany dysregulation of NE function and likely play a key role in the pathophysiology of these neuropsychiatric disorders.

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.

[26] 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.

[27] 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.

[27] 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.

[30] Neurofibrillary tangles, a primary biomarker of Alzheimer's disease, may be found in the locus coeruleus decades before any clinical symptoms.

[17] It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokines and promotes phagocytosis of Aβ.

Evidence appear to support this theory reporting the locus coeruleus integrity primarily responsible of biological brain maintenance,[34] cognitive efficiency, and reduced neuropathological burden.

[38] The locus coeruleus was discovered in 1784 by Félix Vicq-d'Azyr,[39] redescribed later by Johann Christian Reil in 1809[40] and named by the brothers Joseph and Karl Wenzel in 1812.

[52] The official Latin nomenclature, Nomina Anatomica as ratified in Basel in 1895[53] and in Jena in 1935[54][55] contained the orthographically correct form locus caeruleus.

[63] On The Big Bang Theory, season 5, episode 16 ("The Vacation Solution"), Amy tasks Sheldon with removing the locus coeruleus from a tissue sample.