9 Brainy Facts About the Neocortex

Table Of Content

• Extended Data Fig. 12 PCDHγ removal does not affect the basic membrane properties of neocortical excitatory neurons.
• What are the Layers of the Neocortex?
• Common principles between avian, reptilian and mammalian circuits?
• Neurogenesis by Radial Glia
• The Radial Unit Hypothesis
• Development and Evolution of the Human Neocortex

Novel insights about the diversity of progenitor cells and how their neuronal output contributes to build the cerebral cortex are also emerging. Beyond these anatomical differences, even the function of oRG cells has been proposed to be different between human and ferret. In contrast, experiments in the ferret show little evidence for this neurogenic lineage in the OSVZ. Instead, oRG (or IRG) cells served mainly to expand the radial scaffold for neuronal migration and mostly gave rise to astrocytes (Reillo et al., 2010). If these observations are confirmed, the neurogenic and scaffolding roles of RG may need to be considered separately when connecting OSVZ proliferation with neocortical expansion in various species.

Extended Data Fig. 12 PCDHγ removal does not affect the basic membrane properties of neocortical excitatory neurons.

The long-held concept that the leading process of these radially migrating neurons is single and unbranched79,80 has been challenged by new observations, demonstrating frequent branching and thus more complex migratory behaviors than previously reported81. In fact, leading process branching is much more frequent in the developing cortex of ferret than mouse and is related to the tangential displacement of radially migrating neurons. Thus, this seems directly related to the maintenance of the radial organization of the cerebral cortex during the tangential expansion and folding of the neocortex81,82.

What are the Layers of the Neocortex?

Collectively, these talks painted a picture of the diverse behaviors of neural stem and progenitor cells during development and the contribution of these processes to evolution and disease. B, c, Representative 3D reconstruction images of symmetric (b) or asymmetric (c) excitatory neuron clones induced at E12 and analysed at P21. Different coloured dots represent the cell bodies of labelled neurons. The x-/y-/z-axes indicate the spatial orientation of the clone with the x-axis parallel to the brain pial surface and the y-axis perpendicular to the pial surface.

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Common principles between avian, reptilian and mammalian circuits?

But it comprises everything from your spinal cord, and big brain, and so on. Among its functions are to process sensory information and derive language, emotions, and meaningful memories. This localization has been characterized based on a number of factors, including cytoarchitecture, input and output connectivity, proportion of cell types, modular structure, and micro-circuitry.

Neurogenesis by Radial Glia

(B) We highlight the lineage of oRG cells, IP cells, and migrating neurons (red to green) present in the human outer subventricular zone (OSVZ) and the increased number of radial fibers that neurons can use to migrate to the cortical plate. The number of ontogenetic “units” is significantly increased with the addition of oRG cells over ventricular RG (vRG) cells. Short neural precursors (SNP), a transitional cell form between RG and IP cells, are also depicted in (A) and (B). For simplicity, we do not illustrate all of the cell types described in Figure 2E.

For example, neocortical growth and the proposed discontinuity of oRG and vRG basal fibers in humans could negatively affect RA signaling from the meninges, thereby promoting RG cell expansion. Primate corticogenesis is distinguished by the appearance of a large SVZ that has an inner (ISVZ) and outer region (OSVZ), often split by a thin fiber layer (Smart et al., 2002; Zecevic et al., 2005; Fish et al., 2008). Furthermore, thymidine-labeling studies in primates collectively indicate that proliferation of cells within the OSVZ coincides with the major wave of cortical neurogenesis (Rakic, 1974; Lukaszewicz et al., 2005), suggesting that the OSVZ contributes to neuron production. In addition, cells in the OSVZ express RG markers such as nestin (NES), vimentin (VIM), PAX6, and GFAP, as well as the IP cell marker TBR2 (EOMES) (Zecevic et al., 2005; Bayatti et al., 2008; Mo and Zecevic, 2008). But how OSVZ cells expressing RG or IP cell markers related to the known progenitor cell types near the ventricle was not understood. It was hypothesized that the OSVZ contained progenitor cells that were either epithelial cells resembling RG (Fish et al., 2008) or transit-amplifying cells resembling IP cells (Kriegstein et al., 2006).

How unique is the human neocortex?

The effect of progenitor cell expansion on a subsequent increase in neuron number is dependent on the natural counterbalancing relationship between rates of cell proliferation and death. Genetic deletion of key players in the apoptosis pathway in mice results in modest increases to neocortical size and widespread dysregulation of ventricular architecture (reviewed by Kuan et al., 2000). However, even though apoptosis plays a role in normal neocortical development, an evolutionary reduction in cell death during development is unlikely to be a factor that sufficiently explains the great magnitude of neocortical expansion in primates.

A, anterior; Au, auditory; DV, day vision; L, lateral; M, medial; Mo, motor; NV, night vision; P, posterior; SS, somatosensory; V, ventral. While it is tempting and perhaps reasonable to assume that the immediate, nonmammalian ancestors had a dorsal cortex much like that of present-day reptiles, this is far from certain. Early reptiles, now most often called “stem amniotes,” emerged from amphibians about 340 million years ago (mya) and soon divided into two major clades, the sauropsid clade and the synapsid clade.

Although it is not possible to study the development of the human neocortex at the experimental level, major technological breakthroughs in the last few years on stem cell reprogramming and tissue culture offer possibilities that were previously unthinkable. Following the first protocol to generate cerebral organoids from human embryonic stem cells and induced pluripotent stem cells100, these have become the Rosetta stone to study and manipulate human brain development101. Not only can we now grow human cerebral organoids for many months, recapitulating many of the early features of cortical development, but they can be grown to form functional circuits and be responsive to sensory stimuli102. Most importantly, the recent design of a culture protocol to generate highly reproducible cerebral organoids is a fundamental milestone for the consolidation of this as a faithful model of human brain development103.

It had previously been proposed that regions of high and low amounts of SVZ proliferation would predict the future locations of gyri and sulci, respectively (Kriegstein et al., 2006). This connection between progenitor cell behavior during development and shape of the adult brain has recently been examined in ferret, cat, and human neocortex (Reillo et al., 2010). Indeed, regions of future gyral formation contain more proliferating cells in the SVZ during development, and in these areas, proliferation is more pronounced in the OSVZ than in the VZ or ISVZ. The authors of this study experimentally manipulated OSVZ proliferation in the ferret visual cortex by removing thalamic inputs, which resulted in local reduction in neocortical surface area.

Thus, understanding the development of the neocortex benefits from understanding its evolution and disease and also informs about their underlying mechanisms. Here, I briefly summarize the most recent and outstanding advances in our understanding of neocortical development and focus particularly on dorsal progenitors and excitatory neurons. I place special emphasis on the specification of neural stem cells in distinct classes and their proliferation and production of neurons and then discuss recent findings on neuronal migration. Recent discoveries on the genetic evolution of neocortical development are presented with a particular focus on primates. Progress on all these fronts is being accelerated by high-throughput gene expression analyses and particularly single-cell transcriptomics. I end with novel insights into the involvement of microglia in embryonic brain development and how improvements in cultured cerebral organoids are gradually consolidating them as faithful models of neocortex development in humans.

Because the density of fibers did not decrease at the same rate as the fibers were diverging, it was inferred that new fibers are added in basal locations, a property that is likely achieved by the expansion of oRG cells (Reillo et al., 2010). Although neuronal migration on oRG cell fibers has not been directly observed in either ferret or human, the addition of radial fibers by oRG cells is suggested to solve a topological problem—they provide guides for the migration of neurons that can then spread over a greater tangential surface. This condition further supports the overall importance of SVZ progenitor cells in the control of neocortical size.

The neocortex controls language and consciousness, among other things. It is also involved in higher functions such as sensory perception, motor commands, spatial reasoning, and conscious thought. Studies show more than half of all men and one in three women will experience hair loss in their lives.

ORG cells, upon completing mitotic somal translocation, typically divide with a horizontal cleavage plane, with the more basal daughter cell always inheriting the basal fiber. ORG cells were observed to undergo multiple rounds of such divisions, suggesting that these divisions are self-renewing and asymmetric and push the boundary of the OSVZ outward. Cell fate analysis of oRG cell clones confirmed that self-renewed oRG cells remain undifferentiated, whereas oRG cell daughters continue to proliferate and sometimes express markers of neuronal commitment such as TBR2 or ASCL1 (Figure 2B). The radial unit hypothesis described the events of neocortical development only in general terms and did not assume any lineage relationship between RG and neuronal progenitor cells in the ventricular zone (VZ). This conceptual separation was not resolved until a decade ago, as even modern studies reported that the primate VZ contains a heterogeneous population of progenitor cells of which only some express the glial marker GFAP (Levitt et al., 1981). Time-lapse imaging of retrovirally labeled clones demonstrated that RG cells generate neurons by multiple rounds of self-renewing, asymmetric division and that newborn neurons often use the parent cell’s radial fiber to migrate to the cortical plate (Noctor et al., 2001, 2004, 2008).

Immunolabeling for RG and IP cell markers showed that the ferret SVZ contained both types of progenitor cells, with many PAX6-positive cells also exhibiting oRG cell morphology (Fietz et al., 2010; Reillo et al., 2010). Thus, oRG cells (also called intermediate radial glial cells/IRGCs in ferret) and an enlarged SVZ (OSVZ) are not primate-specific features but are also present in carnivores. The cellular mechanisms of human corticogenesis suggest that the outer subventricular zone (OSVZ) contains OSVZ radial glia-like (oRG) cells and an extended lineage of transit-amplifying intermediate progenitor (IP) cells.

Because it is critical in memory consolidation or referred to as “sleep-dependent memory processing.” While you are asleep, the neurons move between rest and depolarizing phase (upstate). You get a good night’s sleep because of the functions of the neocortex. Large mammals and primates have deep grooves enabling the surface area to increase significantly. Group of cells in the embryonic brain that secrete molecules (morphogens) that initiate differential expression of transcription factors that specify formation of the cortical areas. The tissue situated between neuronal cell bodies, composed of a complex network of neuronal and glial processes including dendrites, dendritic spines, axonal terminals and synapses, used often to measure connectedness of a given structure.