The relevance of human fetal subplate zone for developmental neuropathology of neuronal migration disorders and cortical dysplasia

Abstract

The human fetal cerebral cortex develops through a series of partially overlapping histogenetic events which occur in transient cellular compartments, such as the subplate zone. The subplate serves as waiting compartment for cortical afferent fibers, the major site of early synaptogenesis and neuronal differentiation and the hub of the transient fetal cortical circuitry. Thus, the subplate has an important but hitherto neglected role in the human fetal cortical connectome. The subplate is also an important compartment for radial and tangential migration of future cortical neurons. We review the diversity of subplate neuronal phenotypes and their involvement in cortical circuitry and discuss the complexity of late neuronal migration through the subplate as well as its potential relevance for pathogenesis of migration disorders and cortical dysplasia. While migratory neurons may become misplaced within the subplate, they can easily survive by being involved in early subplate circuitry; this can enhance their subsequent survival even if they have immature or abnormal physiological activity and misrouted connections and thus survive into adulthood. Thus, better understanding of subplate developmental history and various subsets of its neurons may help to elucidate certain types of neuronal disorders, including those accompanied by epilepsy.

Keywords: Cortical dysplasia; Disorders of neuronal migration; Human fetal connectome; Radial migration; Tangential migration.

Figure 1

Microphotographs of Golgi stained human fetal somatosensory cortex (Stensaas’ modification of Del Rio Hortega method) in 23 PCW‐old preterm infant. Note the radial orientation of cellular elements in the telencephalic wall (A) due to the presence of radial glia and vertical arrangement of blood vessels; the subplate is recognized as a wide pale zone below the cortical plate (A). The subplate contains postmigratory cortical neurons (B, double arrows), radial glial cells starting to transform into astrocytes (B, arrow) as well as already formed fibrillar astrocytes in contact with blood vessels (B, arrowhead). The subplate contains several types of neurons: polymorphic (C, arrow), fusiform (C, double arrow), and inverted pyramidal (D, arrow). Bar = 1 cm (A) and 200 μm (B, C, D).

Figure 2

Simplified diagram (A) of transient subplate circuitry during the late midfetal period (24–26 PCW). Different presynaptic axons and postsynaptic receptors are represented by different colors (see legends along the diagrams). To enhance the understanding and visibility, three major circuitry systems are displayed separately: monoaminergic (B), thalamocortical (C) and intrinsic subplate plus corticothalamic (D). VZ and SVZ, ventricular and subventricular zone; IZ, intermediate zone; SP, subplate; CP, cortical plate; MZ, marginal zone.