Early history of the locus coeruleus

The first description of the norepinephrine (NE)-containing locus coeruleus (LC) dates back to 1809 in a report by Reil. A depression in the anterior floor of the human fourth ventricle was noted that corresponded with a concentration of blue-black substance just below the tissue surface. The pigmented area remained name-less until 1812 when the Wenzel brothers introduced the term “locus coeruleus.” Today this designation is widely utilized. However, in early investigations, several other names were applied to this melanin-containing group of cells. Arnold, in 1838 and 1851, referred to the LC as the “substantia ferruginea.” Jacobsohn, in 1909, coined the name “nucleus pigmentosus pontis.” In recognition of a cerebellar subcomponent of the LC, Meynert (1872) and Jacobsohn (1909) assigned the classifications “substantia ferruginea superior” and “nucleus pigmentosus tegmento cerebellaris,” respectively. Despite its many names, most studies during this period placed the LC within the dorsolateral portion of the rostral mesencephalic and caudal mesencephalic tegmentum of man and higher primates. Localization of the LC in lower species, such as rodents, was more challenging initially because pigmentation was found to be lacking in areas that were readily observed in higher mammals. Consequently, a considerable amount of uncertainty surrounded the actual position of the LC cell group within these animals. The LC, for example, was once considered to be a caudal extension of the nucleus laterodorsalis tegmenti, a region now acknowledged as a major pontine cholinergic center.