The vast majority of cortical GABAergic neurons can be defined by parvalbumin, somatostatin or calretinin expression. In most mammalians, parvalbumin and somatostatin interneurons have constant proportions, each representing 5–7% of the total neuron number. In contrast, there is a threefold increase in the proportion of calretinin interneurons, which do not exceed 4% in rodents and reach 12% in higher order areas of primate cerebral cortex. In rodents, almost all parvalbumin and somatostatin interneurons originate from the medial part of the subpallial proliferative structure, the ganglionic eminence (GE), while almost all calretinin interneurons originate from its caudal part. The spatial pattern of cortical GABAergic neurons origin from the GE is preserved in the monkey and human brain. However, it could be expected that the evolution is changing developmental rules to enable considerable expansion of calretinin interneuron population. During the early fetal period in primates, cortical GABAergic neurons are almost entirely generated in the subpallium, as in rodents. Already at that time, the primate caudal ganglionic eminence (CGE) shows a relative increase in size and production of calretinin interneurons. During the second trimester of gestation, that is the main neurogenetic stage in primates without clear correlates found in rodents, the pallial production of cortical GABAergic neurons together with the extended persistence of the GE is observed. We propose that the CGE could be the main source of calretinin interneurons for the posterior and lateral cortical regions, but not for the frontal cortex. The associative granular frontal cortex represents around one third of the cortical surface and contains almost half of cortical calretinin interneurons. The majority of calretinin interneurons destined for the frontal cortex could be generated in the pallium, especially in the newly evolved outer subventricular zone that becomes the main pool of cortical progenitors.

In this article we first point at the expansion of associative cortical areas in primates, as well as at the intrinsic changes in the structure of the cortical column. There is a huge increase in proportion of glutamatergic cortical projecting neurons located in the upper cortical layers (II/III). Inside this group, a novel class of associative neurons becomes recognized for its growing necessity in both inter-areal and intra-areal columnar integration. Equally important to the changes in glutamatergic population, we found that literature data suggest a 50% increase in the proportion of neocortical GABAergic neurons between primates and rodents. This seems to be a result of increase in proportion of calretinin interneurons in layers II/III, population which in associative areas represents 15% of all neurons forming those layers. Evaluating data about functional properties of their connectivity we hypothesize that such an increase in proportion of calretinin interneurons might lead to supra-linear growth in memory capacity of the associative neocortical network. An open question is whether there are some new calretinin interneuron subtypes, which might substantially change micro-circuitry structure of the primate cerebral cortex.

The human specific cognitive shift starts around the age of 2 years with the onset of self-awareness, and continues with extraordinary increase in cognitive capacities during early childhood. Diffuse changes in functional connectivity in children aged 2–6 years indicate an increase in the capacity of cortical network. Interestingly, structural network complexity does not increase during this time and, thus, it is likely to be induced by selective maturation of a specific neuronal subclass. Here, we provide an overview of a subclass of cortico-cortical neurons, the associative layer IIIC pyramids of the human prefrontal cortex. Their local axonal collaterals are in control of the prefrontal cortico-cortical output, while their long projections modulate inter-areal processing. In this way, layer IIIC pyramids are the major integrative element of cortical processing, and changes in their connectivity patterns will affect global cortical functioning. Layer IIIC neurons have a unique pattern of dendritic maturation. In contrast to other classes of principal neurons, they undergo an additional phase of extensive dendritic growth during early childhood, and show characteristic molecular changes. Taken together, circuits associated with layer IIIC neurons have the most protracted period of developmental plasticity. This unique feature is advanced but also provides a window of opportunity for pathological events to disrupt normal formation of cognitive circuits involving layer IIIC neurons. In this manuscript, we discuss how disrupted dendritic and axonal maturation of layer IIIC neurons may lead into global cortical disconnectivity, affecting development of complex communication and social abilities. We also propose a model that developmentally dictated incorporation of layer IIIC neurons into maturing cortico-cortical circuits between 2 to 6 years will reveal a previous (perinatal) lesion affecting other classes of principal neurons. This “disclosure” of pre-existing functionally silent lesions of other neuronal classes induced by development of layer IIIC associative neurons, or their direct alteration, could be found in different forms of autism spectrum disorders. Understanding the gene-environment interaction in shaping cognitive microcircuitries may be fundamental for developing rehabilitation and prevention strategies in autism spectrum and other cognitive disorders.

No abstract

In this study we have provided a detailed quantitative morphological analysis of medium spiny neurons (MSNs) in the mice dorsal striatum and determined the consistency of values among three groups of animals obtained in different set of experiments. Dendritic trees of 162 Golgi Cox (FD Rapid GolgiStain Kit) impregnated MSNs from 15 adult C57BL/6 mice were 3-dimensionally reconstructed using Neurolucida software, and parameters of dendritic morphology have been compared among experimental groups. The parameters of length and branching pattern did not show statistically significant difference and were highly consistent among groups. The average neuronal soma surface was between 160 μm2 and 180 μm2, and the cells had 5–6 primary dendrites with close to 40 segments per neuron. Sholl analysis confirmed regular pattern of dendritic branching. The total length of dendrites was around 2100 μm with the average length of individual branching (intermediate) segment around 22 μm and for the terminal segment around 100 μm. Even though each experimental group underwent the same strictly defined protocol in tissue preparation and Golgi staining, we found inconsistency in dendritic volume and soma surface. These changes could be methodologically influenced during the Golgi procedure, although without affecting the dendritic length and tree complexity. Since the neuronal activity affects the dendritic thickness, it could not be excluded that observed volume inconsistency was related with functional states of neurons prior to animal sacrifice. Comprehensive analyses of tree complexity and dendritic length provided here could serve as an additional tool for understanding morphological variability in the most numerous neuronal population of the striatum. As reference values they could provide basic ground for comparisons with the results obtained in studies that use various models of genetically modified mice in explaining different pathological conditions that involve MSNs.