As in the spinal cord, so also in the primitive brain ("urbrain") the perikarya (gray matter) collect around the central fluid space (ependymal canal) while the axons of the neurons (white matter) come to lie peripherally. This basic arrangement is also kept in the brain stem.
Nevertheless, besides the formation of the centrally-situated gray matter in the cerebellum and the cerebral hemispheres, there is an additional development of gray matter in the form of cortex on the surface. In this chapter the generation of the cortex through cell migration is to be explained.
Histogenesis of the cerebral cortex
On the side of the telencephalon two vesicles arise out of which the cerebral hemispheres emerge. Rostrally, after the neuroporus has closed, the neural tube is closed anteriorally by the lamina terminalis.
The prospective cerebral cortex of the pallium develops in the whole roof of the cerebral vesicle while in the thicker floor or subpallium (ventro-lateral region of the cerebral vesicle) the ventricular eminences arise with their medial (stage 14) and lateral (stage 15) portions. The corpus striatum of the telencephalon emerges from the ventricular eminences as well as the core region of the globus pallidus, which belongs to the diencephalon.
Originally the cerebral surface is smooth. After the 18th week, though, it takes on its typical appearance, which is shaped by fissures, sulci (furrows) and gyri (convolutions).
The formation of the cortex is based on the migration of neuroblasts from where they are created in the immediate vicinity of the ventricle space in the direction of the cerebral surface.
The superficial, layered gray matter of the telencephalon, lying below the pia mater, represents the cerebral cortex and the gray matter in the form of cellular collections in the interior form the basal ganglia (core region of the brain stem part). Ascending and descending cortical fibers cross through the ventricular eminences as an internal capsule and divide them into two portions:
- the caudate nucleus inside
- the lentiform nucleus outside
The original layering of the primitive neural tube into three zones (ventricular, intermediate and marginal zones), clearly discernable in the spinal cord, gets blurred in the region of the telencephalon. The neurons of the intermediate zone slowly advance into the marginal zone. In a way that is still incompletely understood, through successive proliferation, migration, and differentiation, they cause the typical six-layered neocortex and the three-layered allocortex to arise.
Radial cell migration
At around the 5th week (stage 14), two layers can be distinguished initially in the wall of the hemisphere vesicles, the ventricular zone and the subpial marginal zone. As was discussed in another place, the proliferation of the stem cells into the ventricular zone leads to the generation of postmitotic neuroblasts and then to the formation of glia cells. The young neuroblasts leave the ventricular zone and, following their emigration, form a further layer, the intermediate zone (mantle layer) (stage 16). Toward the end of the embryonic development (stage 22), at a point in time when the differentiation of the spinal cord is already far advanced, these young neurons wander along special processes of the radial glia out of the intermediate zone. Through this, from the 8th to the 18th weeks, on the inside of the marginal zone they form a further, temporary layer, the cortical plate (voir fig. 41). Indeed the radial glia represents a transitory embryonic cell group out of which, later, a part of the astrocyte population arises.
When the formation of the cortical plate is complete, all of the newly formed neuroblasts in the ventricular zone wander along the radial glia through neurons that have already settled there and accumulate on the outside. This phenomenon is normally referred to as «inside-out layering».
Toward the end of the 6th week (stage 17), the formation of new neuroblast in the ventricular zone decreases and the cell division now takes place more in a proliferations zone between the ventricular zone and the intermediate zone, the so-called subventricular zone. In this zone, until the time of birth, further neurons continue forming that then emigrate into the periphery and form the future cerebral cortex. The accumulated number of layers in the cortex depends on their phylogenetic origin. The maturing of the cortex continues to the end of childhood.
Due to the presence of perikaya the cerebral cortex is referred to as gray matter, while the white matter emerges from the intermediate zone
Cell differentiation of the cerebral cortex is a complex process. Besides a considerable overlap region, it can be divided into two phases
At around the 28th day (stage 10), the neural tube forms. The neuroepithelium is originally a layer of cuboid cells and then slowly becomes multi-layered. After the 5th week (stage 14), the first neuroblasts wander out of the ventricular zone and form the mantle zone. At the beginning of the 6th week (stage 16), the neural tube is thus triple-layered and consists of the ventricular, the intermediate and the marginal zones. Toward the end of the embryonic phase (stage 22), the cortical plate arises through the migration of neuroblasts out of the intermediate and ventricular zones. The ventricular zone gradually stops forming neuroblasts but in the subventricular zone new neurons continue to form (stage 23).
At around the 10th week the ventricular zone differentiates into ependyma. The intermediate zone now contains almost no neuroblasts and slowly delivers the cortical white matter. During the first months of life, the subventricular layer disappears. The molecular layer emerges from the peripheral region of the marginal zone. The various cell layers of the marginal zone that border the cortical plate deliver the gray matter of the cerebral cortex together with them. Depending on which cell types predominate, from the 7th month the formation of the various cortex areas (motor, sensory, associative) each with their specific cytoarchitecture then begins.
Tangential cell migration
At the moment, the mechanisms that steer the tangential migration of the descendents of the ventricular eminences are being intensively researched. The corresponding neurons should reach their target locations along differing pathways, especially along corticifugal fibers. This means that – after they reach the marginal zone – they continue into the intermediate zone and then into the cortical plate. On their way to the cortical plate, they possibly utilize the radial glia, but in a "descending" direction. This would mean that cell movements along the radial glia take place in both directions.
Neocortex and allocortex
From a phylogenic point of view, the cerebral cortex can be divided into the neocortex and allocortex.
The phylogenically older allocortex takes up roughly 10% of the cerebral cortex. It develops early, namely in the 2nd and 3rd months and exhibits 3 to 6 layers. The allocortex is further subdivided into:
transition zone between the neocortex and archicortex. In adults the mesocortex corresponds to the para-hippocampal cortex and the cingulate gyrus (limbic lobe)
(from the Greek archaios = old): triple layered cortex. In adults, it corresponds to the dentate gyrus and the horn of ammon (cornu ammonis; hippocampus)
(from the Greek palaios = ancient): 4 to 6 layered cortex that, like the archicortex, is connected with the olfactory system. In adults the paleocortex is to be met with in the region of the olfactory bulb and the olfactory tubercle as well as in the piriform lobe, and in the entorhinal and prorhinal cortices
The neocortex (from the Greek neos = new) possesses roughly 90% of the cerebral cortex. It develops from the 3rd to 7th months and is characterized by the typical 6 layered cytoarchitecture. It arises initially in the island area (insula) and in the parietal lobes and then spreads into the frontal lobes and the occipital lobes.
The creation of the mature neocortex structures over the course of fetal development is complex and was discussed in the previous chapter.
- The subplate develops with the cortex plate into the cerebral cortex and thus delivers the gray matter of the pallium.
- From the peripheral part of the marginal zone the molecular layer (layer I) emerges.
- The intermediate zone contains hardly any neuroblast cells and delivers the white matter of the pallium.
- Ependyma emerges from the ventricular zone at around the 10th week.
Moreover, from the 7th month, depending on which cell type predominates, the cytoarchitectural particularities of the various regions of the neocortex form (motor, sensory, associative).
Cerebral cortex in brief (human, adult)
- Entire surface area of the adult cortex: 2,200 - 2,400 cm2
- Thickness of the cortex: 1,55 to 4,5 mm
- Cortical neurons: 10 to 16 billion
- The cortex forms 40% of the total mass of the human brain
Brain in brief (human, adult)
- Neurons of the CNS: 100 billion
- Weight: 1300 -1500 g
- Number of synaptic connections: ca. 10,000 per neuron
- Ratio glia cells / neurons in the CNS: 10-50 / 1