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Carla J Shatz - One of the best experts on this subject based on the ideXlab platform.

  • Subplate neurons regulate maturation of cortical inhibition and outcome of ocular dominance plasticity
    2006
    Co-Authors: Patrick O Kanold, Carla J Shatz
    Abstract:

    Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that Subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of Subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without Subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, Subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.

  • role of Subplate neurons in functional maturation of visual cortical columns
    2003
    Co-Authors: Patrick O Kanold, Prakash Kara, Clay R Reid, Carla J Shatz
    Abstract:

    The Subplate forms a transient circuit required for development of connections between the thalamus and the cerebral cortex. When Subplate neurons are ablated, ocular dominance columns do not form in the visual cortex despite the robust presence of thalamic axons in layer 4. We show that Subplate ablation also prevents formation of orientation columns. Visual responses are weak and poorly tuned to orientation. Furthermore, thalamocortical synaptic transmission fails to strengthen, whereas intracortical synapses are unaffected. Thus, Subplate circuits are essential not only for the anatomical segregation of thalamic inputs but also for key steps in synaptic remodeling and maturation needed to establish the functional architecture of visual cortex.

  • selective vulnerability of Subplate neurons after early neonatal hypoxia ischemia
    2003
    Co-Authors: Patrick S. Mcquillen, Carla J Shatz, Ann R Sheldon, Donna M Ferriero
    Abstract:

    Neonatal hypoxia-ischemia in the preterm human leads to selective injury to the subcortical developing white matter, which results in periventricular leukomalacia (PVL), a condition associated with abnormal neurodevelopment. Maturation-dependent vulnerability of late oligodendrocyte progenitors is thought to account for the cellular basis of this condition. A high frequency of cognitive and sensory deficits with decreasing gestational age suggests pervasive abnormalities of cortical development. In a neonatal rat model of hypoxic-ischemic injury that produces the characteristic pattern of subcortical injury associated with human PVL, selective Subplate neuron death is seen. The premature Subplate neuron death occurs after thalamic axons have reached their targets in cortex. Thus, as expected, thalamocortical connections form normally, including patterned connections to somatosensory cortex. However, deficits in motor function still occur, as in babies with PVL. Subplate neuron cell death in PVL provides another mechanism for abnormal neurodevelopment after neonatal hypoxia-ischemia.

  • a novel role for p75ntr in Subplate growth cone complexity and visual thalamocortical innervation
    2002
    Co-Authors: Patrick S. Mcquillen, Michael F Defreitas, Gabriel Zada, Carla J Shatz
    Abstract:

    In cortical development, Subplate axons pioneer the pathway from neocortex to the internal capsule, leading to the proposal that they are required for subsequent area-specific innervation of cortex by thalamic axons. A role for p75 neutrophin receptor (NTR) in area-specific thalamic innervation of cortex is suggested by the observation that p75NTR expression is restricted to Subplate neurons in a low-rostral to high-caudal gradient throughout the period of thalamocortical innervation. In vitro, neurotrophin 3 binding to p75NTR increases neurite length and filopodial formation of immunopurified Subplate neurons, suggesting a role for p75NTR in Subplate growth cone morphology and function in vivo. Consistent with this idea, Subplate growth cones have markedly fewer filopodia in mice lacking p75NTR than in wild type mice. Despite this gross morphologic defect, many Subplate axons in knock-out mice pioneer the projection to the internal capsule as they do in wild-type mice. However a few Subplate axons in the knock-out mice make ectopic projections rostral in the intermediate zone and frontal cortex. Concomitant with the altered morphology of Subplate growth cones, mice lacking p75NTR have diminished innervation of visual cortex from the lateral geniculate nucleus, with markedly reduced or absent connections in 48% of knock-out mice. Thalamic projections to auditory and somatosensory cortex are normal, consistent with the gradient of p75NTR expression. Our present results are unusual in that they argue that p75NTR functions in a novel way in Subplate neurons, that is, in growth cone morphology and function rather than in axon extension or neuronal survival.

  • a novel p75ntr signaling pathway promotes survival not death of immunopurified neocortical Subplate neurons
    2001
    Co-Authors: Michael F Defreitas, Patrick S. Mcquillen, Carla J Shatz
    Abstract:

    Subplate neurons of mammalian neocortex undergo pronounced cell death postnatally, long after they have matured and become incorporated into functional cortical circuits. They express the p75 neurotrophin receptor (p75NTR), which is known to signal cell death in some types of neurons via the activation of sphingomyelinase and the concomitant increase in the sphingolipid ceramide. To evaluate the role of p75NTR in Subplate neurons, they were immunopurified and cultured in vitro . Contrary to its known function as a death receptor, ligand binding to p75NTR promotes Subplate neuron survival. Moreover, p75NTR-dependent survival is blocked by inhibition of ceramide synthesis and rescued by addition of its precursor sphingomyelin. Inhibition of Trk signaling does not block survival, nor is Trk signaling alone sufficient to promote survival. Thus, ligand-dependent p75NTR regulation of the ceramide pathway mediates survival in certain neurons and may represent an important target for neuroprotective drugs in degenerative diseases involving p75NTR-expressing neurons, such as Alzheimer9s disease.

Anna Hoerdersuabedissen - One of the best experts on this subject based on the ideXlab platform.

  • regional scattering of primate Subplate
    2016
    Co-Authors: Zoltan Molnar, Anna Hoerdersuabedissen
    Abstract:

    The Subplate layer is a highly dynamic zone of the developing cerebral cortex that reaches huge proportions in human and nonhuman primates and has been associated with various brain developmental abnormalities. It contains some of the earliest-born neurons of the cortex. Surprisingly, the timing of Subplate neuron birth, migration, distribution, and degree of programmed cell death has only been analyzed in detail in rodents and carnivores, but not in primates. The study by Duque et al. (1) is the first that specifically examines the distribution of Subplate cells labeled with the DNA replication marker tritiated thymidine ([3H]dT) across different brain regions in valuable archived macaque brain material. They show that macaque Subplate neurons, after having completed their migration, become secondarily displaced inward by the arrival of subcortical and cortical axons. Due to regional differences in the magnitude of these developing connections, the Subplate shows remarkable variations in width between different cortical areas. This study adds important and novel insights that may become most relevant in understanding the origin and pathogenesis of human neurodevelopmental disorders. The basic pattern of cortical development was originally described from histological preparations at the beginning of the previous century (reviewed in ref. 2). Transient embryonic cellular compartments including the Subplate zone are generated in the proliferative centers near the ventricular cavity on the center of the brain (reviewed in ref. 3). See Fig. 1 for the distribution of the transient embryonic zones in the human fetus at midgestation and in the macaque at embryonic days 50 and 70 (4). Fig. 1. Compartments and zones of the developing human and macaque cerebral cortex. ( Left ) Schematic coronal section showing the relative location and size of the major compartments within the developing human dorsal cortex at 26 postconception weeks, at the peak of neurogenesis and cell migration. ( Inset … [↵][1]1To whom correspondence should be addressed. Email: zoltan.molnar{at}dpag.ox.ac.uk. [1]: #xref-corresp-1-1

  • development evolution and pathology of neocortical Subplate neurons
    2015
    Co-Authors: Anna Hoerdersuabedissen, Zoltan Molnar
    Abstract:

    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.

  • Subplate in a rat model of preterm hypoxia ischemia
    2014
    Co-Authors: Wei Zhi Wang, Anna Hoerdersuabedissen, Franziska M Oeschger, Chika Okusa, Vanessa Ginet, Tomohiro Matsuyama, Anita C Truttmann, Zoltan Molnar
    Abstract:

    Objective Hypoxia–ischemia (HI) in preterm infants primarily leads to injuries in the cerebral white matter. However, there is growing evidence that perinatal injury in preterms can also involve other zones including the cortical gray matter. In a neonatal rat model of HI, selective vulnerability of Subplate has been suggested using BrdU birth-dating methods. In this study, we aimed to investigate the neuropathological changes of the Subplate and deep layers of the cortex following cerebral HI in neonatal rats with specific cell markers. Methods P2 rats underwent permanent occlusion of the right common carotid artery followed by a period of hypoxia. P8 rats were analyzed using immunohistochemistry; Subplate and deep layers cells were quantified and compared with sham-operated case. Results A large variability in the extent of the cerebral injury was apparent. For the three analyzed Subplate populations (Nurr1+, Cplx3+, and Ctgf+ cells), no significant cell reduction was observed in mild and moderate cases. Only in severe cases, Subplate cells were strongly affected, but these injuries were always accompanied by the cell reductions in layers VI and V. Interpretation We could therefore not confirm a specific vulnerability of Subplate cells compared to other deep layers or the white matter in our model.

  • extracortical origin of some murine Subplate cell populations
    2014
    Co-Authors: Maria Pedraza, Anna Hoerdersuabedissen, Zoltan Molnar, Maria Amparo Albertmaestro, Juan A De Carlos
    Abstract:

    The Subplate layer, the deepest cortical layer in mammals, has important roles in cerebral cortical development. The Subplate contains heterogeneous cell populations that are morphologically diverse, with several projection targets. It is currently assumed that these cells are generated in the germinative zone of the earliest cortical neuroepithelium. Here we identify a pallial but extracortical area located in the rostromedial telencephalic wall (RMTW) that gives rise to several cell populations. Postmitotic neurons migrate tangentially from the RMTW toward the cerebral cortex. Most RMTW-derived cells are incorporated into the Subplate layer throughout its rostrocaudal extension, with others contributing to the GABAergic interneuron pool of cortical layers V and VI.

  • molecular diversity of early born Subplate neurons
    2013
    Co-Authors: Anna Hoerdersuabedissen, Zoltan Molnar
    Abstract:

    Subplate cells in the mouse are generally defined as cells located in the Subplate layer between the white matter and layer 6a. They are some of the earliest born and maturing cells of the cerebral cortex. The postnatal Subplate layer in mouse contains neurons with expression of the presynaptic protein complexin 3 (Cplx3), connective tissue growth factor (CTGF), the orphan nuclear receptor Nr4a2 (Nurr1), and the G-protein-coupled lysophosphatidic acid receptor 1 (Lpar1/Edg2). All 4 of these molecular markers show layer 6b-restricted expression at young postnatal ages, with CTGF expression being the most widespread in the young postnatal Subplate. However, all 4 markers overlap in their expression pattern to varying degrees. Here we demonstrate with bromodeoxyuridine birthdating that cells labeled with any 1 of these molecular Subplate markers are indeed generated at E11.5 or E12.5 in the mouse. Furthermore, we demonstrate a correlation between gene expression and cell birthdates. Lpar1-GFP cells are preferentially generated on E11.5, whereas Cplx3 or Nurr1-positive cells are equally generated during the 2-day peak of Subplate neurogenesis (E11.5–E12.5). Our study also demonstrates that early-born Subplate neurons labeled by Cplx3, Nurr1, and Lpar1-GFP survive preferentially after the first postnatal week compared with other Subplate neurons.

Zoltan Molnar - One of the best experts on this subject based on the ideXlab platform.

  • regional scattering of primate Subplate
    2016
    Co-Authors: Zoltan Molnar, Anna Hoerdersuabedissen
    Abstract:

    The Subplate layer is a highly dynamic zone of the developing cerebral cortex that reaches huge proportions in human and nonhuman primates and has been associated with various brain developmental abnormalities. It contains some of the earliest-born neurons of the cortex. Surprisingly, the timing of Subplate neuron birth, migration, distribution, and degree of programmed cell death has only been analyzed in detail in rodents and carnivores, but not in primates. The study by Duque et al. (1) is the first that specifically examines the distribution of Subplate cells labeled with the DNA replication marker tritiated thymidine ([3H]dT) across different brain regions in valuable archived macaque brain material. They show that macaque Subplate neurons, after having completed their migration, become secondarily displaced inward by the arrival of subcortical and cortical axons. Due to regional differences in the magnitude of these developing connections, the Subplate shows remarkable variations in width between different cortical areas. This study adds important and novel insights that may become most relevant in understanding the origin and pathogenesis of human neurodevelopmental disorders. The basic pattern of cortical development was originally described from histological preparations at the beginning of the previous century (reviewed in ref. 2). Transient embryonic cellular compartments including the Subplate zone are generated in the proliferative centers near the ventricular cavity on the center of the brain (reviewed in ref. 3). See Fig. 1 for the distribution of the transient embryonic zones in the human fetus at midgestation and in the macaque at embryonic days 50 and 70 (4). Fig. 1. Compartments and zones of the developing human and macaque cerebral cortex. ( Left ) Schematic coronal section showing the relative location and size of the major compartments within the developing human dorsal cortex at 26 postconception weeks, at the peak of neurogenesis and cell migration. ( Inset … [↵][1]1To whom correspondence should be addressed. Email: zoltan.molnar{at}dpag.ox.ac.uk. [1]: #xref-corresp-1-1

  • development evolution and pathology of neocortical Subplate neurons
    2015
    Co-Authors: Anna Hoerdersuabedissen, Zoltan Molnar
    Abstract:

    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.

  • Subplate in a rat model of preterm hypoxia ischemia
    2014
    Co-Authors: Wei Zhi Wang, Anna Hoerdersuabedissen, Franziska M Oeschger, Chika Okusa, Vanessa Ginet, Tomohiro Matsuyama, Anita C Truttmann, Zoltan Molnar
    Abstract:

    Objective Hypoxia–ischemia (HI) in preterm infants primarily leads to injuries in the cerebral white matter. However, there is growing evidence that perinatal injury in preterms can also involve other zones including the cortical gray matter. In a neonatal rat model of HI, selective vulnerability of Subplate has been suggested using BrdU birth-dating methods. In this study, we aimed to investigate the neuropathological changes of the Subplate and deep layers of the cortex following cerebral HI in neonatal rats with specific cell markers. Methods P2 rats underwent permanent occlusion of the right common carotid artery followed by a period of hypoxia. P8 rats were analyzed using immunohistochemistry; Subplate and deep layers cells were quantified and compared with sham-operated case. Results A large variability in the extent of the cerebral injury was apparent. For the three analyzed Subplate populations (Nurr1+, Cplx3+, and Ctgf+ cells), no significant cell reduction was observed in mild and moderate cases. Only in severe cases, Subplate cells were strongly affected, but these injuries were always accompanied by the cell reductions in layers VI and V. Interpretation We could therefore not confirm a specific vulnerability of Subplate cells compared to other deep layers or the white matter in our model.

  • extracortical origin of some murine Subplate cell populations
    2014
    Co-Authors: Maria Pedraza, Anna Hoerdersuabedissen, Zoltan Molnar, Maria Amparo Albertmaestro, Juan A De Carlos
    Abstract:

    The Subplate layer, the deepest cortical layer in mammals, has important roles in cerebral cortical development. The Subplate contains heterogeneous cell populations that are morphologically diverse, with several projection targets. It is currently assumed that these cells are generated in the germinative zone of the earliest cortical neuroepithelium. Here we identify a pallial but extracortical area located in the rostromedial telencephalic wall (RMTW) that gives rise to several cell populations. Postmitotic neurons migrate tangentially from the RMTW toward the cerebral cortex. Most RMTW-derived cells are incorporated into the Subplate layer throughout its rostrocaudal extension, with others contributing to the GABAergic interneuron pool of cortical layers V and VI.

  • molecular diversity of early born Subplate neurons
    2013
    Co-Authors: Anna Hoerdersuabedissen, Zoltan Molnar
    Abstract:

    Subplate cells in the mouse are generally defined as cells located in the Subplate layer between the white matter and layer 6a. They are some of the earliest born and maturing cells of the cerebral cortex. The postnatal Subplate layer in mouse contains neurons with expression of the presynaptic protein complexin 3 (Cplx3), connective tissue growth factor (CTGF), the orphan nuclear receptor Nr4a2 (Nurr1), and the G-protein-coupled lysophosphatidic acid receptor 1 (Lpar1/Edg2). All 4 of these molecular markers show layer 6b-restricted expression at young postnatal ages, with CTGF expression being the most widespread in the young postnatal Subplate. However, all 4 markers overlap in their expression pattern to varying degrees. Here we demonstrate with bromodeoxyuridine birthdating that cells labeled with any 1 of these molecular Subplate markers are indeed generated at E11.5 or E12.5 in the mouse. Furthermore, we demonstrate a correlation between gene expression and cell birthdates. Lpar1-GFP cells are preferentially generated on E11.5, whereas Cplx3 or Nurr1-positive cells are equally generated during the 2-day peak of Subplate neurogenesis (E11.5–E12.5). Our study also demonstrates that early-born Subplate neurons labeled by Cplx3, Nurr1, and Lpar1-GFP survive preferentially after the first postnatal week compared with other Subplate neurons.

Miloš Judaš - One of the best experts on this subject based on the ideXlab platform.

  • the relevance of human fetal Subplate zone for developmental neuropathology of neuronal migration disorders and cortical dysplasia
    2015
    Co-Authors: Ivica Kostovic, Goran Sedmak, Mario Vuksic, Miloš Judaš
    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.

  • developmental history of the Subplate zone Subplate neurons and interstitial white matter neurons relevance for schizophrenia
    2011
    Co-Authors: Ivica Kostovic, Miloš Judaš, Goran Sedmak
    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.

  • early history of Subplate and interstitial neurons from theodor meynert 1867 to the discovery of the Subplate zone 1974
    2010
    Co-Authors: Miloš Judaš, Goran Sedmak, Mihovil Pletikos
    Abstract:

    In this historical review, we trace the early history of research on the fetal Subplate zone, Subplate neurons and interstitial neurons in the white matter of the adult nervous system. We arrive at several general conclusions. First, a century of research clearly testifies that interstitial neurons, Subplate neurons and the Subplate zone were first observed and variously described in the human brain – or, in more general terms, in large brains of gyrencephalic mammals, characterized by an abundant white matter and slow and protracted prenatal and postnatal development. Secondly, the Subplate zone cannot be meaningfully defined using a single criterion – be it a specific population of cells, fibres or a specific molecular or genetic marker. The Subplate zone is a highly dynamic architectonic compartment and its size and cellular composition do not remain constant during development. Thirdly, it is important to make a clear distinction between the Subplate zone and the Subplate (and interstitial) neurons. The transient existence of the Subplate zone (as a specific architectonic compartment of the fetal telencephalic wall) should not be equated with the putative transient existence of Subplate neurons. It is clear that in rodents, and to an even greater extent in humans and monkeys, a significant number of Subplate cells survive and remain functional throughout life.

  • populations of Subplate and interstitial neurons in fetal and adult human telencephalon
    2010
    Co-Authors: Miloš Judaš, Goran Sedmak, Mihovil Pletikos, Natasa Jovanovmilosevic
    Abstract:

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal Subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal Subplate neurons cannot be regarded as interstitial, because the Subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the ‘waiting’ compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input–output connectivity. However, although the Subplate zone is a transient fetal structure, many Subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from Subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular) interstitial neurons in the postnatal and adult deep cerebral white matter (i.e. corpus callosum, anterior commissure, internal and external capsule and the corona radiata/centrum semiovale). Although these deep interstitial neurons are poorly developed or absent in the brains of rodents, they represent a prominent feature of the significantly enlarged white matter of human and non-human primate brains.

  • the development of the Subplate and thalamocortical connections in the human foetal brain
    2010
    Co-Authors: Ivica Kostovic, Miloš Judaš
    Abstract:

    UNLABELLED The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the 'waiting' period with transient cortical Subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous Subplate and sensory-driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. CONCLUSION Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the Subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.

Ivica Kostovic - One of the best experts on this subject based on the ideXlab platform.

  • the relevance of human fetal Subplate zone for developmental neuropathology of neuronal migration disorders and cortical dysplasia
    2015
    Co-Authors: Ivica Kostovic, Goran Sedmak, Mario Vuksic, Miloš Judaš
    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.

  • involvement of the Subplate zone in preterm infants with periventricular white matter injury
    2014
    Co-Authors: Ivica Kostovic, Ivana Pogledic, Catherine Falletbianco, Homa Adlebiassette, Pierre Gressens, Catherine Verney
    Abstract:

    Studies of periventricular white matter injury (PWMI) in preterm infants suggest the involvement of the transient cortical Subplate zone. We studied the cortical wall of non-cystic and cystic PWMI cases and controls. Non-cystic PWMI corresponded to diffuse white matter lesions, the predominant injury currently detected by imaging. Glial cell populations were analyzed in post-mortem human frontal lobes from very preterm [24–29 postconceptional weeks (pcw)] and preterm infants (30–34 pcw) using immunohistochemistry for glial fibrillary acidic protein (GFAP), monocarboxylate transporter 1 (MCT1), ionized calcium-binding adapter molecule 1 (Iba1), CD68 and oligodendrocyte lineage (Olig2). Glial activation extended into the Subplate in non-cystic PWMI but was restricted to the white matter in cystic PWMI. Two major age-related and laminar differences were observed in non-cystic PWMI: in very preterm cases, activated microglial cells were increased and extended into the Subplate adjacent to the lesion, whereas in preterm cases, an astroglial reaction was seen not only in the Subplate but throughout the cortical plate. There were no differences in Olig2-positive pre-oligodendrocytes in the Subplate in PWMI cases compared with controls. The involvement of gliosis in the deep Subplate supports the concept of the complex cellular vulnerability of the Subplate zone during the preterm period and may explain widespread changes in magnetic resonance signal intensity in early PWMI.

  • developmental history of the Subplate zone Subplate neurons and interstitial white matter neurons relevance for schizophrenia
    2011
    Co-Authors: Ivica Kostovic, Miloš Judaš, Goran Sedmak
    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.

  • the development of the Subplate and thalamocortical connections in the human foetal brain
    2010
    Co-Authors: Ivica Kostovic, Miloš Judaš
    Abstract:

    UNLABELLED The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the 'waiting' period with transient cortical Subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous Subplate and sensory-driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. CONCLUSION Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the Subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.

  • laminar organization of the human fetal cerebrum revealed by histochemical markers and magnetic resonance imaging
    2002
    Co-Authors: Ivica Kostovic, Miloš Judaš, Marko Rados, Pero Hrabac
    Abstract:

    The developing human cerebrum displays age-specific changes in its patterns of lamination. Among these, the Subplate zone is the most prominent transient compartment because growing major afferent systems temporarily reside in this zone, establish synapses and take part in cellular interactions that are crucial for subsequent cortical development. We explored the potential of magnetic resonance imaging (MRI) for tracing the developmental history of the most prominent cortical layer (the Subplate zone) and other laminar compartments of the fetal cerebral wall between 15 and 36 weeks post-ovulation. We found that changes in the MRI lamination pattern of the human fetal cerebral wall are predominantly caused by changes in the Subplate zone. Histochemical staining of the extracellular matrix (ECM) enables selective visualization of the Subplate zone and correlation with an increase in MRI signal intensity in the Subplate zone and ingrowth and accumulation of thalamocortical and corticocortical afferents and their subsequent relocation to the cortical plate. Thus, dynamic changes in the MRI appearance of the Subplate zone and histochemical staining of its ECM can be used as indirect parameters for an assessment of normal versus disturbed unfolding of crucial histogenetic events that are involved in prenatal shaping of the human cerebral cortex.