The human locus coeruleus 3-D stereotactic anatomy

Abstract

The human LC is a nucleus thinner and longer than previously described (in average 14.5 mm long and 2-2.5 mm thick), localized 1 mm under the IV ventricle, 3 mm apart from the midline and centered 14-21 mm above de ponto-medullary junction. No correlation was found between LC and pons dimensions, the gender or the age.

Higher rostral locus coeruleus integrity is associated with better memory performance in older adults

“…In particular, we pooled over aligned scans to facilitate LC delineation at a group level 58 , which in turn was used to restrict automatized extraction of individual peak intensities 64,65 . The LC volume of interest (search space) generated at the group level matches recent histological analyses that reported a dense packing of noradrenergic cells in a thin central LC compartment and dispersion towards rostral and especially caudal extremities 14 . We demonstrated high validity of the proposed semiautomatic procedure by comparisons to both previously published LC maps 41,58 and manual LC intensity ratings (see Supplemental results).…”

“…Its location adjacent to the ventricular system and its widespread, unmyelinated projections expose LC cells to blood-and cerebrospinal-fluid bound toxins, making them a likely target for neurodegeneration 34 . Consistent with its age-related vulnerability, a prominent, rostrally accentuated decline of LC density was reported in healthy aging (see Manaye and colleagues 18 for a review of early studies; but see 12,14,35,36 and Mather and Harley 34 for a recent discussion). Based on longitudinal data, Wilson and colleagues 10 reported initial evidence pointing to the importance of LC integrity, here assessed via LC's neuronal density, for maintaining memory abilities in old age.…”

“…Neuromelanin accumulates non-linearly in LC cells across life with a peak concentration at around 50-60 years of age and subsequent stable levels 35 or decline, probably due to preferential loss of pigmented cells 42,43 . Thus, neuromelanin forms a reliable natural contrast agent, particularly in older adults, that can be harnessed in cell count 14 and MRI studies 48 to index LC integrity. However, neuromelanin may be a less effective indicator of LC structure in younger adults due to the many LC neurons that do not yet contain neuromelanin, based on post-mortem analyses using tyrosine hydroxylase (i.e., the rate-limiting enzyme in NE synthesis) as a marker of LC neurons 18 .…”

“…The LC is a hyperpigmented cylindrical cluster of catecholaminergic neurons located in the dorsorostral tegmentum 13 . Roughly symmetrical in both hemispheres, it extends for only about 15 mm rostrocaudally from the level of the inferior colliculi to a position in the lateral wall of the fourth ventricle 14,15 . Despite its small size, the LC has diffuse and highly arborized efferent projections throughout the brain 16 .…”

Differential involvement of brainstem noradrenergic and midbrain dopaminergic nuclei in cognitive control

“…Nieuwenhuys [] suggested that the cell groups A4 and A6 form the LC complex, whereas other authors suggested the cell groups A4–A7 [Pearson et al, ]. The LC proper was described as a bilateral, “tube‐like,” pigmented nucleus [Fernandes et al, ; German et al, ]. It begins rostrally in the caudolateral part of the mesencephalic central gray, at the level of the inferior colliculus (A6), and extends caudally to a position in the lateral wall of the fourth ventricle (A4) [German, et al, ].…”