The cortex of primates is relatively expanded compared with many other mammals, yet little is known about what developmental processes account for the expansion of cortical subtype numbers in primates, including humans. We asked whether GABAergic and pyramidal neuron production occurs for longer than expected in primates than in mice in a sample of 86 developing primate and rodent brains. We use high-resolution structural, diffusion MR scans and histological material to compare the timing of the ganglionic eminences (GE) and cortical proliferative pool (CPP) maturation between humans, macaques, rats, and mice. We also compare the timing of post-neurogenetic maturation of GABAergic and pyramidal neurons in primates (i.e. humans, macaques) relative to rats and mice to identify whether delays in neurogenesis are concomitant with delayed post-neurogenetic maturation. We found that the growth of the GE and CPP are both selectively delayed compared with other events in primates. By contrast, the timing of post-neurogenetic GABAergic and pyramidal events (e.g. synaptogenesis) are predictable from the timing of other events in primates and in studied rodents. The extended duration of GABAergic and pyramidal neuron production is associated with the amplification of GABAerigc and pyramidal neuron numbers in the human and non-human primate cortex.

To uncover the ontogenesis of the human indusium griseum (IG), 28 post-mortem fetal human brains, 12–40 postconceptional weeks (PCW) of age, and 4 adult brains were analyzed immunohistochemically and compared with post-mortem magnetic resonance imaging (MRI) of 28 fetal brains (14–41 PCW). The morphogenesis of the IG occurred between 12 and 15 PCW, transforming the bilateral IG primordia into a ribbon-like cortical lamina. The histogenetic transition of sub-laminated zones into the three-layered cortical organization occurred between 15 and 35 PCW, concomitantly with rapid cell differentiation that occurred from 18 to 28 PCW and the elaboration of neuronal connectivity during the entire second half of gestation. The increasing number of total cells and neurons in the IG at 25 and 35 PCW confirmed its continued differentiation throughout this period. High-field 3.0 T post-mortem MRI enabled visualization of the IG at the mid-fetal stage using T2-weighted sequences. In conclusion, the IG had a distinct histogenetic differentiation pattern than that of the neighboring intralimbic areas of the same ontogenetic origin, and did not show any signs of regression during the fetal period or postnatally, implying a functional role of the IG in the adult brain, which is yet to be disclosed.

BACKGROUND AND PURPOSE: In subjects with agenesis of the corpus callosum, a variety of structural brain alterations is already present during prenatal life. Quantification of these alterations in fetuses with associated brain or body malformations (corpus callosum agenesis and other related anomalies) and so-called isolated cases may help to optimize the challenging prognostic prenatal assessment of fetuses with corpus callosum agenesis. This fetal MR imaging study aimed to identify differences in the size of the prenatal hippocampus between subjects with isolated corpus callosum agenesis, corpus callosum agenesis and other related anomalies, and healthy controls. MATERIALS AND METHODS: Eighty-five in utero fetal brain MR imaging scans, (20-35 gestational weeks) were postprocessed using a high-resolution algorithm. On the basis of multiplanar T2-TSE sequences, 3D isovoxel datasets were generated, and both hippocampi and the intracranial volume were segmented. RESULTS: Hippocampal volumes increased linearly with gestational weeks in all 3 groups. One-way ANOVA demonstrated differences in hippocampal volumes between control and pathologic groups (isolated corpus callosum agenesis: left, P ϭ .02; right, P ϭ .04; corpus callosum agenesis and other related anomalies: P Ͻ .001). Differences among the pathologic groups were also present for both sides. Intracranial volume and right and left hippocampal volume ratios were different between corpus callosum agenesis cases and controls (P Ͻ .001). When we corrected for intracranial volume, no differences were found between corpus callosum agenesis and other associated anomalies and isolated corpus callosum agenesis (left, P ϭ .77; right, P ϭ .84). Hippocampal size differences were more pronounced at a later gestational age. CONCLUSIONS: Callosal agenesis apparently interferes with the normal process of hippocampal formation and growth, resulting in underdevelopment, which could account for certain learning and memory deficits in individuals with agenesis of the corpus callosum in later life. ABBREVIATIONS: aACC ϭ corpus callosum agenesis and other associated anomalies; ACC ϭ agenesis of the corpus callosum; GW ϭ gestational weeks; HF ϭ hippocampal formation; iACC ϭ isolated agenesis of the corpus callosum; ICV ϭ intracranial volume

Little is known about the development of the human entorhinal cortex (EC), a major hub in a widespread network for learning and memory, spatial navigation, high‐order processing of object information, multimodal integration, attention and awareness, emotion, motivation, and perception of time. We analyzed a series of 20 fetal and two adult human brains using Nissl stain, acetylcholinesterase (AChE) histochemistry, and immunocytochemistry for myelin basic protein (MBP), neuronal nuclei antigen (NeuN), a pan‐axonal neurofilament marker, and synaptophysin, as well as postmortem 3T MRI. In comparison with other parts of the cerebral cortex, the cytoarchitectural differentiation of the EC begins remarkably early, in the 10th week of gestation (w.g.). The differentiation occurs in a superficial magnocellular layer in the deep part of the marginal zone, accompanied by cortical plate (CP) condensation and multilayering of the deep part of CP. These processes last until the 13–14th w.g. At 14 w.g., the superficial lamina dissecans (LD) is visible, which divides the CP into the lamina principalis externa (LPE) and interna (LPI). Simultaneously, the rostral LPE separates into vertical cell‐dense islands, whereas in the LPI, the deep LD emerges as a clear acellular layer. In the 16th w.g., the LPE remodels into vertical cell‐dense and cell‐sparse zones with a caudorostral gradient. At 20 w.g., NeuN immunoreactivity is most pronounced in the islands of layer II cells, whereas migration and differentiation inside‐out gradients are seen simultaneously in both the upper (LPE) and the lower (LPI) pyramidal layers. At this stage, the EC adopts for the first time an adult‐like cytoarchitectural organization, the superficial LD becomes discernible by 3T MRI, MBP‐expressing oligodendrocytes first appear in the fimbria and the perforant path (PP) penetrates the subiculum to reach its molecular layer and travels along through the Cornu Ammonis fields to reach the suprapyramidal blade of the dentate gyrus, whereas the entorhinal‐dentate branch perforates the hippocampal sulcus about 2–3 weeks later. The first AChE reactivity appears as longitudinal stripes at 23 w.g. in layers I and II of the rostrolateral EC and then also as AChE‐positive in‐growing fibers in islands of superficial layer III and layer II neurons. At 40 w.g., myelination of the PP starts as patchy MBP‐immunoreactive oligodendrocytes and their processes. Our results refute the possibility of an inside‐out pattern of the EC development and support the key role of layer II prospective stellate cells in the EC lamination. As the early cytoarchitectural differentiation of the EC is paralleled by the neurochemical development, these developmental milestones in EC structure and connectivity have implications for understanding its normal function, including its puzzling modular organization and potential contribution to consciousness content (awareness), as well as for its insufficiently explored deficits in developmental, psychiatric, and degenerative brain disorders.

The subthalamic nucleus (STN) is a small, ovoid structure, and an important site of deep brain stimulation (DBS) for the treatment of Parkinson’s disease. Although the STN is a clinically important structure, there are many unresolved issues with regard to it. These issues are especially related to the anatomical subdivision, neuronal phenotype, neuronal composition, and spatial distribution. In this study, we have examined the expression pattern of 8 neuronal markers [nNOS, NeuN, parvalbumin (PV), calbindin (CB), calretinin (CR), FOXP2, NKX2.1, and PAX6] in the adult human STN. All of the examined markers, except CB, were present in the STN. To determine the neuronal density, we have performed stereological analysis on Nissl-stained and immunohistochemical slides of positive markers. The stereology data were also used to develop a three-dimensional map of the spatial distribution of neurons within the STN. The nNOS population exhibited the largest neuronal density. The estimated total number of nNOS STN neurons is 281,308 ± 38,967 (± 13.85%). The STN neuronal subpopulations can be divided into two groups: one with a neuronal density of approximately 3,300 neurons/mm3 and the other with a neuronal density of approximately 2,200 neurons/mm3. The largest density of STN neurons was observed along the ventromedial border of the STN and the density gradually decreased toward the dorsolateral border. In this study, we have demonstrated the presence of 7 neuronal markers in the STN, three of which were not previously described in the human STN. The human STN is a collection of diverse, intermixed neuronal subpopulations, and our data, as far as the cytoarchitectonics is concerned, did not support the tripartite STN subdivision.