Evidence for a Postnatal Doubling of Neuron Number in the Developing Human Cerebral Cortex Between 15 Months and 6 Years

Abstract

The generalization of the finding of no postnatal neurogenesis in non-human primates to humans may be incorrect because: (1) rhesus macaques belong to a superfamily that diverged more than 25 million years ago from the superfamily including the genus Homo; (2) the pulse thymidine labeling method, which demonstrates DNA synthesis rather than mitosis per se, is less reliable than some have assumed. This study examines changes in the number of neurons in a column underneath a cortical surface area of 1 mm2, extending through all cortical layers (mm2-column) for 35 gyri (representing about 73% of the human cerebral cortex) based on the data of J.L. Conel (1939 to 1967). We corrected these data, derived from his measures of cortical neuronal packing density, somal breadth and height, and cortical layer thickness at postnatal ages 0, 1, 3, 6, 15, 24, 48, and 72 months, for shrinkage and stereological errors. In all 35 gyri, neuron number/mm2-column: (1) initially declines (μ=46% decline, σ=8%), 95% of which is due to surface area expansion (mean age of nadir value=15.8 months); (2) then increases to age 72 months by 70% (μ=1.7-fold increase, (μ rate=1.1% per month). Because of a concomitant 1.3-fold increase in cortical surface from 15 to 72 months, total cortical neuron number increases 2.2-fold. The close agreement between neuron number/mm2-column for Comel's age 72-month data to the corresponding values reported by others for adult human and primate cortex using more modern methods suggests the finding is not an artifact. Neuronal proliferative fate-determining factors provide at least four mechanisms for increasing cortical neuron number postnatally, with or without DNA synthesis.