Friday, August 19, 2011

Neotony - how long does our pre-frontal cortex stay young?

When I first looked at the title "Extraordinary neoteny of synaptic spines in the human prefrontal cortex", I excitedly thought "Great, I'm going to learn that my 69 year old prefrontal cortex is still crafting and pruning synapses." Alas, by extraordinary, the authors mean that they have determined that the 2-3 fold decrease in the density of dendritic spines previously thought to be largely complete by the end of adolescence continues well into the third decade of life before stabilizing at the adult level.
The major mechanism for generating diversity of neuronal connections beyond their genetic determination is the activity-dependent stabilization and selective elimination of the initially overproduced synapses [Changeux JP, Danchin A (1976) Nature 264:705–712]. The largest number of supranumerary synapses has been recorded in the cerebral cortex of human and nonhuman primates. It is generally accepted that synaptic pruning in the cerebral cortex, including prefrontal areas, occurs at puberty and is completed during early adolescence [Huttenlocher PR, et al. (1979) Brain Res 163:195–205]. In the present study we analyzed synaptic spine density on the dendrites of layer IIIC cortico–cortical and layer V cortico–subcortical projecting pyramidal neurons in a large sample of human prefrontal cortices in subjects ranging in age from newborn to 91 y. We confirm that dendritic spine density in childhood exceeds adult values by two- to threefold and begins to decrease during puberty. However, we also obtained evidence that overproduction and developmental remodeling, including substantial elimination of synaptic spines, continues beyond adolescence and throughout the third decade of life before stabilizing at the adult level. Such an extraordinarily long phase of developmental reorganization of cortical neuronal circuitry has implications for understanding the effect of environmental impact on the development of human cognitive and emotional capacities as well as the late onset of human-specific neuropsychiatric disorders.

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