Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc Natl Acad Sci U S A

Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10,000 Zagreb, Croatia.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2011; 108(32):13281-6. DOI: 10.1073/pnas.1105108108
Source: PubMed


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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    • "DEVELOPMENT transplantation into mouse, and only develop axons, dendrites and functional synapses several months after transplantation (Fig. 5C) (Espuny-Camacho et al., 2013; Kirkeby et al., 2012; Maroof et al., 2013; Nicholas et al., 2013). This pattern of protracted maturation is strikingly reminiscent of the situation in the developing human brain, where neurons take months and sometimes years to reach maturation; this might underlie some of the relative neoteny that characterizes human brain maturation, particularly in specific cortical areas (DeFelipe, 2011; Petanjek et al., 2011). Overall, these data point to cell-intrinsic mechanisms that control a 'clock' of neuronal maturation and connectivity. "
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    • "Techniques commonly used in humans to study brain organization such as EEG, MEG, and MRI lack cellular resolution. Molecular and histological approaches using postmortem human brain material have limitations to unravel extensive subcellular architecture, since typically , only partial cellular morphologies can be resolved and quantitative analysis is performed on subcompartments of the apical/basal dendritic tree (Braak 1980; Ong and Garey 1990; Elston et al. 2001; Jacobs et al. 2001; Anderson et al. 2009; Petanjek et al. 2011; Rosoklija et al. 2014). Additionally, postmortem delays to brain tissue fixation may effect morphology of fine cellular structures (de Ruiter and Uylings 1987; Swaab and Uylings 1988; Oberheim et al. 2009). "
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