title: Developmental history of the subplate zone, subplate neurons and interstitial white matter neurons: relevance for schizophrenia.
abstract: The subplate zone is a transient cytoarchitectonic compartment of the fetal telencephalic wall and contains a population of subplate neurons which are the main neurons of the fetal neocortex and play a key role in normal development of cerebral cortical structure and connectivity. While the subplate zone disappears during the perinatal and early postnatal period, numerous subplate neurons survive and remain embedded in the superficial (gyral) white matter of adolescent and adult brain as so-called interstitial neurons. In both fetal and adult brain, subplate/interstitial neurons belong to two major classes of cortical cells: (a) projection (glutamatergic) neurons and (b) local circuit (GABAergic) interneurons. As interstitial neurons remain strategically positioned at the cortical/white matter interface through which various cortical afferent systems enter the deep cortical layers, they probably serve as auxiliary interneurons involved in differential "gating" of cortical input systems. It is widely accepted that prenatal lesions which alter the number of surviving subplate neurons (i.e., the number of interstitial neurons) and/or the nature of their involvement in cortical circuitry represent an important causal factor in pathogenesis of at least some types of schizophrenia--e.g., in the subgroup of patients with cognitive impairment and deficits of frontal lobe functions. The abnormal functioning of cortical circuitry in schizophrenia becomes manifest during the adolescence, when there is an increased demand for proper functioning of the prefrontal cortex. In this review, we describe developmental history of subplate zone, subplate neurons and surviving interstitial neurons, as well as presumed consequences of the increased number of GABAergic interstitial neurons in the prefrontal cortex. We propose that the increased number of GABAergic interstitial neurons leads to the increased inhibition of prefrontal cortical neurons. This inhibitory action of GABAergic interstitial neurons is facilitated by their strategic position at the cortical/white matter interface where limbic and modulatory afferent pathways enter the prefrontal cortex. Thus, enlarged population of inhibitory interstitial neurons (even if they represent a minor fraction of total neuron number, as in the cerebral cortex itself) may alter the differential "gating" of limbic and modulatory inputs (as well as other cortical and subcortical inputs) and cause a functional disconnectivity between the prefrontal and limbic cortex in the adolescent brain. In conclusion, fetal subplate neurons and surviving postnatal interstitial neurons are important modulators of cortical functions in both normal and schizophrenic cerebral cortex.
authors.affiliation: Section of Developmental Neuroscience, Croatian Institute for Brain Research, Department of Neuroscience, University of Zagreb School of Medicine, Šalata 12, 10000 Zagreb, Croatia. ikostov@hiim.hr
authors.forename: Ivica
authors.initials: I
authors.lastname: Kostović
authors.forename: Miloš
authors.initials: M
authors.lastname: Judaš
authors.forename: Goran
authors.initials: G
authors.lastname: Sedmak
mesh_terms: D002465:Cell Movement / Q000502:physiology; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D013687:Telencephalon / Q000033:anatomy & histology* / Q000196:embryology* / Q000254:growth & development*