Quantitative and Phylogenetic Analyses of Immature Neurons in Cortical Layer II and Amygdala of Macaque Monkeys

Highlights What are the main findings? What are the implications of the main findings?Highlights What are the main findings? What are the implications of the main findings?Abstract "Immature" or "late-maturing" neurons exist in layer II of the cerebral cortex (cortical immature neurons; cINs) and within the amygdaloid complex (subcortical immature neurons; scINs). These cells remain in a prolonged state of arrested development yet retain the ability to resume maturation and to functionally integrate into neural circuits. Both cINs and scINs are abundant in large-brained mammals with respect to small-brained, lissencephalic rodents. In previous reports, using a comparable method for quantification in diverse mammals, including mice, chimpanzees, and other species, we showed positive correlation of immature neuron cell density with brain size and gyrencephaly. Here, we quantified the cINs and scINs in the cerebral cortex and amygdala of young adult rhesus macaques to determine how they compare to phylogenetic variation. Our results further demonstrate the existence of covariance between cIN density and both increasing brain size and neocortical expansion, as well as the specialized increase of scINs in the amygdala of primates. These findings support the emerging view that immature neurons may represent a reservoir of undifferentiated (stem cell-independent) neuronal cells for the widely expanded cortices and amygdala of mammals endowed with high-order cognitive functions and complex sociality. The detailed mapping of cortical and subcortical immature neurons in a primate often used in translational research sets the foundation for deeper, functional studies aimed at understanding human brain plasticity.