The subplate zone is a highly dynamic structure that contains diverse cell populations that are derived from cortical (ventricular and subventricular zones) and extracortical (rostro-medial telencephalic wall and ganglionic eminence) sources. Interneurons may be underrepresented in the postnatal subplate.
Subplate cells in rodents and primates share similarities, such as an early birth date and their location below the cortical plate, but they exhibit marked differences in relative cell survival times, molecular expression profiles and cell morphologies.
Subplate cells pioneer axonal projections from the cortex to subcortical targets, but there are species differences in the targets that they innervate.
Ablation of the subplate by excitotoxicity or immunotoxicity impairs circuit-level maturation of the primary sensory cortex, and an absence of subplate neurons prevents thalamic afferents from crossing the pallial–subpallial boundary and invading the cortex.
Transcriptomic evidence highlights the relative maturity of embryonic and fetal subplate cells and suggests novel roles for subplate neurons in the secretion of various extracellular molecules involved in axon pathfinding, cell survival or differentiation, and synaptic plasticity.
Histological, MRI and transcriptomic evidence points towards a role for the subplate in schizophrenia and autism. Whether this is causal or a consequence of earlier malformations remains unclear.
Subplate neurons have an essential role in cortical circuit formation. They are among the earliest formed neurons of the cerebral cortex, are located at the junction of white and grey matter, and are necessary for correct thalamocortical axon ingrowth. Recent transcriptomic studies have provided opportunities for monitoring and modulating selected subpopulations of these cells. Analyses of mouse lines expressing reporter genes have demonstrated novel, extracortical subplate neurogenesis and have shown how subplate cells are integrated under the influence of sensory activity into cortical and extracortical circuits. Recent studies have revealed that the subplate is involved in neurosecretion and modification of the extracellular milieu.
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The authors thank R. Guillery and K. Korrell for their thoughtful comments on an earlier version of this manuscript. Our laboratory is supported by grants from the UK Medical Research Council (G0700377 and G00900901), the UK Biotechnology and Biological Sciences Research Council (B/I021833/1) and the Wellcome Trust (092071/Z/10/Z). Z.M. received support from St John's College Research Centre, Oxford.
The authors declare no competing financial interests.
Cells projecting across the corpus callosum or located within the corpus callosum, a fibre tract connecting the two cerebral hemispheres.
'Smooth' brains; that is, those without ridges (gyri) or crevices (sulci) on the surface.
- Cajal–Retzius cells
Early-born neurons of the cortical anlage that express a secreted molecule called reelin, which is essential for normal cortical lamination to occur.
(BrdU). A synthetic analogue of the nucleic acid thymidine that incorporates into DNA during replication and repair. It can subsequently be detected by immunohistochemistry and is used to label cells during the DNA replication stage (S phase) of cell division.
- Barrel hollows
The cell-sparse centre of each 'barrel' of cells in the barrel cortex. Thalamic afferents cluster inside this cylinder of cells.
- Barrel septa
This is the region in between adjacent barrel walls.
- First-order thalamic nuclei
The thalamic nuclei that receive direct innervation from the sensory periphery.
- Higher-order thalamic nuclei
The thalamic nuclei with a cortico-cortical relay function that receive the majority of extrinsic excitatory input from the cerebral cortex.
- Barrel field
The mouse and rat barrel field is the somatosensory region of the cerebral cortex that receives input from the whiskers. The name derives from the 'barrel-like' cylindrical cell arrangement in layer 4.
Clusters of cells or neurons in abnormal locations.
- Rice–Vannucci model
A rodent model of perinatal hypoxia injury obtained by ligation of the common carotid artery on one side of the body followed by a period of low oxygen in the inspired air.
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Hoerder-Suabedissen, A., Molnár, Z. Development, evolution and pathology of neocortical subplate neurons. Nat Rev Neurosci 16, 133–146 (2015). https://doi.org/10.1038/nrn3915
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