The enigmatic fetal subplate compartment forms an early tangential cortical nexus and provides the framework for construction of cortical connectivity

The most prominent transient compartment of the primate fetal cortex is the deep, cell-sparse, synapse-containing subplate compartment (SPC). The developmental role of the SPC and its extraordinary size in humans remain enigmatic. This paper evaluates evidence on the development and connectivity of the SPC and discusses its role in the pathogenesis of neurodevelopmental disorders. A synthesis of data shows that the subplate becomes a prominent compartment by its expansion from the deep cortical plate (CP), appearing well-delineated on MR scans and forming a tangential nexus across the hemisphere, consisting of an extracellular matrix, randomly distributed postmigratory neurons, multiple branches of thalamic and long corticocortical axons. The SPC generates early spontaneous non-synaptic and synaptic activity and mediates cortical response upon thalamic stimulation. The subplate nexus provides large-scale interareal connectivity possibly underlying fMR resting-state activity, before corticocortical pathways are established. In late fetal phase, when synapses appear within the CP, transient the SPC coexists with permanent circuitry. The histogenetic role of the SPC is to provide interactive milieu and capacity for guidance, sorting, waiting and target selection of thalamocortical and corticocortical pathways. The new evolutionary role of the SPC and its remnant white matter neurons is linked to the increasing number of associative pathways in the human neocortex. These roles attributed to the SPC are regulated using a spatiotemporal gene expression during critical periods, when pathogenic factors may disturb vulnerable circuitry of the SPC, causing neurodevelopmental cognitive circuitry disorders.