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

ABSTRACT 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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Available from: Harry Uylings, Sep 29, 2015
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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. "
    Development 09/2015; 142(18):3138-3150. DOI:10.1242/dev.120568 · 6.46 Impact Factor
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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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    ABSTRACT: The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on "full" human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of "full" human neuron morphologies and present direct evidence that human neurons are not "scaled-up" versions of rodent or macaque neurons, but have unique structural and functional properties. © The Author 2015. Published by Oxford University Press.
    Cerebral Cortex 08/2015; DOI:10.1093/cercor/bhv188 · 8.67 Impact Factor
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    • "r social awareness , introspection , planning , making decisions , focusing and goal - directed behavior ( Bechara et al . , 2000 ; Fleming et al . , 2012 ) . While the highest levels of synaptic density and remodeling in the prefrontal cortex are found in adolescence in humans , they only stabilize at adult levels between 30 and 40 years of age ( Petanjek et al . , 2011 ) ."
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    ABSTRACT: It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use) strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse) leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes in line with Neolamarckian concepts of evolution (Packard, 1901). Evidence is presented of bipartite evolutionary processes-Darwinian and Neolamarckian-driving human descent from a common ancestor shared with the great apes.
    Frontiers in Neuroscience 06/2015; 9:209. DOI:10.3389/fnins.2015.00209 · 3.66 Impact Factor
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