Talk:Neural System - Postnatal

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Cite this page: Hill, M.A. (2019, June 26) Embryology Neural System - Postnatal. Retrieved from


Comparison of cortical folding measures for evaluation of developing human brain

Neuroimage. 2016 Jan 15;125:780-90. doi: 10.1016/j.neuroimage.2015.11.001. Epub 2015 Nov 6.

Shimony JS1, Smyser CD2, Wideman G3, Alexopoulos D4, Hill J5, Harwell J6, Dierker D7, Van Essen DC8, Inder TE9, Neil JJ10.


We evaluated 22 measures of cortical folding, 20 derived from local curvature (curvature-based measures) and two based on other features (sulcal depth and gyrification index), for their capacity to distinguish between normal and aberrant cortical development. Cortical surfaces were reconstructed from 12 term-born control and 63 prematurely-born infants. Preterm infants underwent 2-4 MR imaging sessions between 27 and 42weeks postmenstrual age (PMA). Term infants underwent a single MR imaging session during the first postnatal week. Preterm infants were divided into two groups. One group (38 infants) had no/minimal abnormalities on qualitative assessment of conventional MR images. The second group (25 infants) consisted of infants with injury on conventional MRI at term equivalent PMA. For both preterm infant groups, all folding measures increased or decreased monotonically with increasing PMA, but only sulcal depth and gyrification index differentiated preterm infants with brain injury from those without. We also compared scans obtained at term equivalent PMA (36-42weeks) for all three groups. No curvature-based measured distinguished between the groups, whereas sulcal depth distinguished term control from injured preterm infants and gyrification index distinguished all three groups. When incorporating total cerebral volume into the statistical model, sulcal depth no longer distinguished between the groups, though gyrification index distinguished between all three groups and positive shape index distinguished between the term control and uninjured preterm groups. We also analyzed folding measures averaged over brain lobes separately. These results demonstrated similar patterns to those obtained from the whole brain analyses. Overall, though the curvature-based measures changed during this period of rapid cerebral development, they were not sensitive for detecting the differences in folding associated with brain injury and/or preterm birth. In contrast, gyrification index was effective in differentiating these groups. Copyright © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Brain injury; Cortical curvature; Cortical folding; Premature infant

PMID 26550941


Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period

Nature. 2014 Jan 16;505(7483):407-11. doi: 10.1038/nature12821. Epub 2013 Dec 4.

Whiteus C1, Freitas C2, Grutzendler J1. Author information


During the neonatal period, activity-dependent neural-circuit remodelling coincides with growth and refinement of the cerebral microvasculature. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affects cortical microvascular development. Unexpectedly, chronic stimulation by repetitive sounds, whisker deflection or motor activity led to a near arrest of angiogenesis in barrel, auditory and motor cortices, respectively. Chemically induced seizures also caused robust reductions in microvascular density. However, altering neural activity in adult mice did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather to reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences for brain development, function and pathology. Comment in Development: hyperactively restricting angiogenesis. [Nat Rev Neurosci. 2014]

PMID 24305053


Accurate and consistent segmentation of infant brain MR images plays an important role in quantifying patterns of early brain development, especially in longitudinal studies. However, due to rapid maturation and myelination of brain tissues in the first year of life, the intensity contrast of gray and white matter undergoes dramatic changes. In fact, the contrast inverse around 6–8 months of age, when the white and gray matter tissues are isointense and hence exhibit the lowest contrast, posing significant challenges for segmentation algorithms. In this paper, we propose a longitudinally guided level set method to segment serial infant brain MR images acquired from 2 weeks up to 1.5 years of age, including the isointense images. At each single-time-point, the proposed method makes optimal use of T1, T2 and the diffusion-weighted images for complimentary tissue distribution information to address the difficulty caused by the low contrast. Moreover, longitudinally consistent term, which constrains the distance across the serial images within a biologically reasonable range, is employed to obtain temporally consistent segmentation results. Application of our method on 28 longitudinal infant subjects, each with 5 longitudinal scans, shows that the automated segmentations from the proposed method match the manual ground-truth with much higher Dice Ratios than other single-modality, single-time-point based methods and the longitudinal but voxel-wise based methods. The software of the proposed method is publicly available in NITRC (




The temporal pattern of postnatal neurogenesis found in the neocortex of the Göttingen mini pig brain

Neuroscience. 2011 Aug 19. [Epub ahead of print]

Hou J, Eriksen N, Pakkenberg B. Source Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital, 2400 Copenhagen NV, Denmark.


The Göttingen minipig (G-mini) is increasingly used as a non-primate model for human neurological diseases. We applied design-based stereology on five groups of G-minis aged 1 day, 14 days, 30 days, 100 days, and 2 years or older to estimate the pattern of postnatal neuron number development in the neocortex. Two time periods for the postnatal increase of neocortical neuron number were observed from the time of birth to day 14 (P=0.013) and from day 30 to day 100 (P<0.001). No significant change in neuron number was found from day 14to 30 (P=0.58) and day 100 onward (P=0.39). The average estimated total number of neurons in the neocortex was 236, 274, 264, 338, and 353 million, respectively. Since neurogenesis and neuronal migration in the human neocortex are generally accepted to be complete before term, the application of G-mini as human disease models may be inappropriate before day 100. However, G-mini may serve as a valuable model for the studies of ongoing neurogenesis in the living brain.

Copyright © 2011. Published by Elsevier Ltd.

PMID 21878372

Remodeling of monoplanar Purkinje cell dendrites during cerebellar circuit formation

PLoS One. 2011;6(5):e20108. Epub 2011 May 31.

Kaneko M, Yamaguchi K, Eiraku M, Sato M, Takata N, Kiyohara Y, Mishina M, Hirase H, Hashikawa T, Kengaku M. Source Laboratory for Neural Cell Polarity, RIKEN Brain Science Institute, Wako, Saitama, Japan.


Dendrite arborization patterns are critical determinants of neuronal connectivity and integration. Planar and highly branched dendrites of the cerebellar Purkinje cell receive specific topographical projections from two major afferent pathways; a single climbing fiber axon from the inferior olive that extend along Purkinje dendrites, and parallel fiber axons of granule cells that contact vertically to the plane of dendrites. It has been believed that murine Purkinje cell dendrites extend in a single parasagittal plane in the molecular layer after the cell polarity is determined during the early postnatal development. By three-dimensional confocal analysis of growing Purkinje cells, we observed that mouse Purkinje cells underwent dynamic dendritic remodeling during circuit maturation in the third postnatal week. After dendrites were polarized and flattened in the early second postnatal week, dendritic arbors gradually expanded in multiple sagittal planes in the molecular layer by intensive growth and branching by the third postnatal week. Dendrites then became confined to a single plane in the fourth postnatal week. Multiplanar Purkinje cells in the third week were often associated by ectopic climbing fibers innervating nearby Purkinje cells in distinct sagittal planes. The mature monoplanar arborization was disrupted in mutant mice with abnormal Purkinje cell connectivity and motor discoordination. The dendrite remodeling was also impaired by pharmacological disruption of normal afferent activity during the second or third postnatal week. Our results suggest that the monoplanar arborization of Purkinje cells is coupled with functional development of the cerebellar circuitry.

PMID 21655286

Immunohistological markers for proliferative events, gliogenesis, and neurogenesis within the adult hippocampus

Cell Tissue Res. 2011 Jul;345(1):1-19. Epub 2011 Jun 7.

von Bohlen und Halbach O. Source Institute of Anatomy and Cell Biology, Ernst Moritz Arndt University of Greifswald, Friedrich Loeffler Strasse 23c, Greifswald, Germany.


Biologists long believed that, once development is completed, no new neurons are produced in the forebrain. However, as is now firmly established, new neurons can be produced at least in two specific forebrain areas: the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation. Neurogenesis within the adult DG occurs constitutively throughout postnatal life, and the rate of neurogenesis within the DG can be altered under various physiological and pathophysiological conditions. The process of adult neurogenesis within the DG is a multi-step process (proliferation, differentiation, migration, targeting, and synaptic integration) that ends with the formation of a post-mitotic functionally integrated new neuron. Various markers are expressed during specific stages of adult neurogenesis. The availability of such markers allows the time-course and fate of newly born cells to be followed within the DG in a detailed and precise fashion. Several of the available markers (e.g., PCNA, Ki-67, PH3, MCM2) are markers for proliferative events, whereas others are more specific for early phases of neurogenesis and gliogenesis within the adult DG (e.g., nestin, GFAP, Sox2, Pax6). In addition, markers are available allowing events to be distinguished that are related to later steps of gliogenesis (e.g., vimentin, BLBP, S100beta) or neurogenesis (e.g., NeuroD, PSA-NCAM, DCX).

PMID 21647561


Developmental changes in cerebral grey and white matter volume from infancy to adulthood.

Int J Dev Neurosci. 2010 Oct;28(6):481-9. Epub 2010 Jun 30. Groeschel S, Vollmer B, King MD, Connelly A.

Radiology and Physics Unit, UCL Institute of Child Health, London, UK. Abstract

In order to quantify human brain development in vivo, high resolution magnetic resonance images of 158 normal subjects from infancy to young adulthood were studied (age range 3 months-30 years, 71 males, 87 females). Data were analysed using algorithms based on voxel-based morphometry (VBM) (an objective whole brain processing technique) to generate global volume measures of whole brain, grey matter (GM) and white matter (GM). Gender-specific development of WM and GM volumes is characterised using a piecewise polynomial growth curve model to account for the non-linear nature of human brain development, implemented using Markov chain Monte Carlo simulation. The statistical method employed in this study proved to be successful and robust in the characterisation of brain development. The resulting growth curve parameter estimates lead to the following observations: total brain volume is demonstrated to undergo an initial rapid spurt. The total GM volume peaks during childhood and decreases thereafter, whereas total WM volume increases up to young adulthood. Relative to brain size, GM decreases and WM increases markedly over this age range in a non-linear manner, resulting in an increasing WM-to-GM ratio over much of the observed age range. In addition, significant gender differences are found. In general, brain volume and total white and grey matter volume are larger in males than in females, with a time-dependent difference over the age range studied. Over part of the observed age range females tend to have more GM volume relative to brain size and lower WM-to-GM ratio than males. The presented findings should be taken into account when investigating physiological and pathological changes during brain development.


Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS

Nature. 2009 Dec 24;462(7276):1065-9. Epub 2009 Dec 13.

Tran TS, Rubio ME, Clem RL, Johnson D, Case L, Tessier-Lavigne M, Huganir RL, Ginty DD, Kolodkin AL. Source Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. Abstract The majority of excitatory synapses in the mammalian CNS (central nervous system) are formed on dendritic spines, and spine morphology and distribution are critical for synaptic transmission, synaptic integration and plasticity. Here, we show that a secreted semaphorin, Sema3F, is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (Npn-2, also known as Nrp2) and plexin A3 (PlexA3, also known as Plxna3), exhibit increased dentate gyrus (DG) granule cell (GC) and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn-2(-/-) brain slices cortical layer V and DG GCs exhibit increased mEPSC (miniature excitatory postsynaptic current) frequency. In contrast, a distinct Sema3A-Npn-1/PlexA4 signalling cascade controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. These disparate effects of secreted semaphorins are reflected in the restricted dendritic localization of Npn-2 to apical dendrites and of Npn-1 (also known as Nrp1) to all dendrites of cortical pyramidal neurons. Therefore, Sema3F signalling controls spine distribution along select dendritic processes, and distinct secreted semaphorin signalling events orchestrate CNS connectivity through the differential control of spine morphogenesis, synapse formation, and the elaboration of dendritic morphology.

PMID 20010807

Heterogeneity in subcortical brain development: A structural magnetic resonance imaging study of brain maturation from 8 to 30 years.

J Neurosci. 2009 Sep 23;29(38):11772-82.

Ostby Y, Tamnes CK, Fjell AM, Westlye LT, Due-Tønnessen P, Walhovd KB.

Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Norway. Abstract Brain development during late childhood and adolescence is characterized by decreases in gray matter (GM) and increases in white matter (WM) and ventricular volume. The dynamic nature of development across different structures is, however, not well understood, and the present magnetic resonance imaging study took advantage of a whole-brain segmentation approach to describe the developmental trajectories of 16 neuroanatomical volumes in the same sample of children, adolescents, and young adults (n = 171; range, 8-30 years). The cerebral cortex, cerebral WM, caudate, putamen, pallidum, accumbens area, hippocampus, amygdala, thalamus, brainstem, cerebellar GM, cerebellar WM, lateral ventricles, inferior lateral ventricles, third ventricle, and fourth ventricle were studied. The cerebral cortex was further analyzed in terms of lobar thickness and surface area. The results revealed substantial heterogeneity in developmental trajectories. GM decreased nonlinearly in the cerebral cortex and linearly in the caudate, putamen, pallidum, accumbens, and cerebellar GM, whereas the amygdala and hippocampus showed slight, nonlinear increases in GM volume. WM increased nonlinearly in both the cerebrum and cerebellum, with an earlier maturation in cerebellar WM. In addition to similarities in developmental trajectories within subcortical regions, our results also point to differences between structures within the same regions: among the basal ganglia, the caudate showed a weaker relationship with age than the putamen and pallidum, and in the cerebellum, differences were found between GM and WM development. These results emphasize the importance of studying a wide range of structural variables in the same sample, for a broader understanding of brain developmental principles.


A structural MRI study of human brain development from birth to 2 years.

Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, Hamer RM, Lin W, Gerig G, Gilmore JH. J Neurosci. 2008 Nov 19;28(47):12176-82.

PMID: 19020011