The Superior Function of the Subplate in Early Neocortical Development

Abstract

During early development the structure and function of the cerebral cortex is critically organized by subplate neurons (SPNs), a mostly transient population of glutamatergic and GABAergic neurons located below the cortical plate. At the molecular and morphological level SPNs represent a rather diverse population of cells expressing a variety of genetic markers and revealing different axonal-dendritic morphologies. Electrophysiologically SPNs are characterized by their rather mature intrinsic membrane properties and firing patterns. They are connected via electrical and chemical synapses to local and remote neurons, e.g., thalamic relay neurons forming the first thalamocortical input to the cerebral cortex. Therefore SPNs are robustly activated at pre- and perinatal stages by the sensory periphery. Although SPNs play pivotal roles in early neocortical activity, development and plasticity, they mostly disappear by programmed cell death during further maturation. On the one hand, SPNs may be selectively vulnerable to hypoxia-ischemia contributing to brain damage, on the other hand there is some evidence that enhanced survival rates or alterations in SPN distribution may contribute to the etiology of neurological or psychiatric disorders. This review aims to give a comprehensive and up-to-date overview on the many functions of SPNs during early physiological and pathophysiological development of the cerebral cortex.

Keywords: connectivity; development; neocortex; pathology; plasticity; review; subplate.

FIGURE 1

Appearance of the SP in developing human and mouse cerebral cortex. (A) Cresylviolet (left) and Nissl (right) stained sections from human fetal cortex at postconceptional weeks 18 and 22–24, respectively (modified with permission from Kostovic et al. (2002) and Judas et al. (2013). Note that the thickness of the SP exceeds that of the CP. (B) Nissl stained sections of the mouse cortex at E18.5 and P1 (modified with permission from Hayano et al., 2014). Note that SPNs represent a small band of neurons below the cortical plate/layer 6. (C) Immunhistochemical processed section of a P8 mouse cortex illustrating that Cplx3-positive Neurons are located exclusively in the SP (with permission from Hoerder-Suabedissen et al., 2009). (D) Nurr1 antibodies also stains exclusively SPNs (with permission from Hoerder-Suabedissen et al., 2009). Scale bars 1 mm in (A) and 100 μm in (B–D). MZ, marginal zone; CP, cortical plate; SP, subplate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone; V and VI, layer V and VI, respectively.

FIGURE 2

Synaptic connectivity of SPNs. (A) Intracellular biocytin staining of one SPN (arrow) in P3 mouse neocortex reveals columnar arrangement of several dye-coupled cells (with permission from Dupont et al., 2006). (B) Representative firing pattern induced by suprathreshold depolarization of SPN in P2 mouse cortex. SPNs were identified by their location, their appearance in differential interference contrast videomicroscopic image, and their electrophysiological properties. (C) Glutamatergic PSCs elicited by electrical stimulation in the thalamus. (D) GABAergic PSCs induced by electrical stimulation of the SP. (E) Schematic drawing illustrating SPN inputs (top) and outputs (bottom). CP, cortical plate; CR, Cajal-Retzius neuron in the marginal zone (MZ).