Locus coeruleus

The Locus ceruleus, also spelled locus caeruleus or locus coeruleus (Latin for 'the blue spot'), is a nucleus in the brain stem responsible for physiological responses to stress and panic.

The locus ceruleus (or "LC") resides on the dorsal wall of the upper pons, under the cerebellum in the caudal midbrain, surrounded by the fourth ventricle. This nucleus is one of the main sources of norepinephrine in the brain, and is composed of mostly medium-sized 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 locus ceruleus was first discovered by Félix Vicq-d'Azyr.

Anatomical 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, via its branches, the entire cerebral cortex.

As the main homeostatic control center of the brain, the locus ceruleus 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 ceruleus receives inputs from a number of other brain regions, primarily:
 * Medial prefrontal cortex. The connection is constant, excitatory, and increases in strength with raised activity levels in the subject.
 * Nucleus paragigantocellularis. This region integrates autonomic and environmental stimuli.
 * Nucleus prepositus hypoglossi. This region is involved in gaze.
 * Lateral hypothalamus. This releases orexin which, as well as its other functions, is excitatory in the locus ceruleus.

Function
The locus ceruleus is widely 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 ceruleus 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.

Linguistic Notes
Caeruleus is the classical Latin spelling, and coeruleus a slightly rarer archaic form. The spelling ceruleus, formed by contraction of the diphthongs ae or oe into e, is the modernized form.