Evolution of increased glia-neuron ratios in the human frontal cortex

Abstract

Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia-neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia-neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as "theory of mind" (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.

Fig. 1.

Glial cell distributions in anthropoid primates. (A) The allometric scaling of species mean glial cell density (cells per cubed millimeter) against neuron density (cells per cubed millimeter) in layer II/III of area 9L in anthropoid primates. A solid line represents the LS regression line that is fit to the nonhuman anthropoids based on species mean data (y = 0.68x + 1.54; r = 0.534; P = 0.027). A dashed line represents the LS regression line that is fit to independent contrasts mapped back into “tip” species space, calculated to predict a hypothetical species attached to the branch leading to humans by pruning humans from the tree and rerooting it. It should be noted that absolute values for cell densities may show some error from fixation artifact; however, because each individual data point is affected by such error equally in both x and y, the slope and residuals are reliable. (B) The allometric scaling of the glia–neuron ratio against brain weight in layer II/III of area 9L in anthropoid primates. A solid line represents the LS regression line that is fit to the nonhuman species mean data (y = 0.23x − 0.47; r = 0.804; P < 0.001). A dashed line represents the LS regression line that is fit to independent contrasts mapped back into tip species space with humans pruned from the tree. (C) Glia–neuron ratio across frontal areas in humans, chimpanzees, and macaque monkeys (n = 6 for each species), showing means and 95% CIs.

Fig. 2.

Nissl staining of neurons and glia from different species in layer II/III of area 9L. Arrows indicate examples of neurons, and arrowheads indicate examples of glia. Aotus trivirgatus (A), Saguinus oedipus (B), Alouatta caraya (C), Pithecia pithecia (D), Trachypithecus francoisi (E), Colobus angolensis (F), Cercopithecus kandti (G), Hylobates muelleri (H), and Pongo pygmaeus (I). (Scale bar, 50 μm.)