Extraordinary neoteny of synaptic spines in the human prefrontal cortex

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

On the predictability of supramolecular interactions in molecular cocrystals-the view from the bench

A series of cocrystals involving theophylline and fluorobenzoic acids highlights the difficulty of predicting supramolecular interactions in molecular crystals.MKC and DKB gratefully acknowledge financial support from the UCL Faculty of Mathematical and Physical Sciences. DKB and WJ thank the Royal Society for a Newton International Fellowship and the Isaac Newton Trust (Trinity College, University of Cambridge) for funding. MA thanks the EPSRC for a studentship, while SAS acknowledges funding through the EPSRC CASE scheme with Pfizer. We are grateful for computational support from the UK national high performance computing service, ARCHER, for which access was obtained via the UKCP consortium and funded by EPSRC grant (EP/K013564/1).This is the final version of the article. It first appeared from the Royal Society of Chemistry via https://doi.org//10.1039/C6CE00293

Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall

Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8-40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a "triplet" structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented "corridors" of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain

Adult structure and development of the human fronto-opercular cerebral cortex (Broca's region)

Broca's area encompasses opercular and triangular part of the inferior frontal gyrus, covered by Brodmann's areas 44 and 45, respectively. Recent neuroimaging studies have revealed that, in addition to classical language functions, Broca's area has novel and unexpected functions, serving as a likely interface of action and perception important for both verbal and nonverbal communication. In this review, we focus on structural features of Broca's area in adult and developing human brain. We emphasize that: (a) in terms of architectonic classification, Broca's area displays a dual nature by virtue of its intermediate position between agranular motor-premotor cortex and granular prefrontal associative cortex; and (b) numerous studies of morphological asymmetries are of limited value for understanding neurobiological basis of functions implemented by Broca's area. Finally, we summarize findings from our ongoing study on postnatal development of two defining cytoarchitectonic features of Broca's area in the adult brain, magnopyramidality (meaning that pyramidal neurons in layer III are larger than those in layer V) and dysgranularity (meaning that cortical layer IV is present, but poorly developed). We conclude that areal specification of areas 44 and 45 requires at least 2 (and probably 3) years of postnatal life for its gradual completion