Comparative anatomy of the locus coeruleus in humans and nonhuman primates

Abstract

The locus coeruleus (LC) is a dense cluster of neurons that projects axons throughout the neuroaxis and is located in the rostral pontine tegmentum extending from the level of the inferior colliculus to the motor nucleus of the trigeminal nerve. LC neurons are lost in the course of several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. In this study we used Nissl staining and tyrosine hydroxylase (TH) immunoreactivity to compare the human LC with that of closely related primate species, including great and lesser apes, and macaque monkeys. TH catalyzes the initial and rate-limiting step in catecholamine biosynthesis. The number of TH-immunoreactive (TH-ir) neurons was estimated in each species using stereologic methods. In the LC of humans the mean total number of TH-ir neurons was significantly higher compared to the other primates. Because the total number of TH-ir neurons in the LC was highly correlated with the species mean volume of the medulla oblongata, cerebellum, and neocortical gray matter, we conclude that much of the observed phylogenetic variation can be explained by anatomical scaling. Notably, the total number of LC neurons in humans was most closely predicted by the nonhuman allometric scaling relationship relative to medulla size, whereas the number of LC neurons in humans was considerably lower than predicted according to neocortex and cerebellum volume.

Figure 1

Photomicrograph through the LC showing TH-ir neurons; (A) human (B), chimpanzee, (C) gorilla, (D) gibbon, (E) rhesus Monkey. Bar = 200 μm, SCP (superior cerebellar peduncle), MV (nucleus of the mesencephalic tract of trigeminal nerve), SubC (nucleus subcoeruleus).

Figure 2

LC neuron number versus medulla volume (A), cerebellum volume (B), and neocortex volume (C). The solid lines represent the least-squares regression of nonhuman species mean data. The dotted lines represent the least-squares regression of nonhuman phylogenetic independent contrasts plotted in contemporary “tip” species data space.

Figure 3

Graph showing the estimated number of TH-ir neurons in the examined primate species. Data show means and SD.