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Alterations to Dendritic Spine Morphology, but Not Dendrite Patterning, of Cortical Projection Neurons in Tc1 and Ts1Rhr Mouse Models of Down Syndrome

Haas, MA; Bell, D; Slender, A; Lana-Elola, E; Watson-Scales, S; Fisher, EMC; Tybulewicz, VLJ; (2013) Alterations to Dendritic Spine Morphology, but Not Dendrite Patterning, of Cortical Projection Neurons in Tc1 and Ts1Rhr Mouse Models of Down Syndrome. Plos One , 8 (10) , Article e78561. 10.1371/journal.pone.0078561. Green open access

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[thumbnail of TIFF Figure 1. Hsa21, orthologous mouse chromosome regions and relevant DS mouse models]
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[thumbnail of TIFF Figure 2. The distribution of GFP-electroporated neurons in Tc1 and Ts1Rhr mouse cortex]
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[thumbnail of TIFF Figure 3. Layer II–IV cortical projection neuron morphology in Tc1 and Ts1Rhr mice]
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[thumbnail of TIFF Figure 4. Dendritic spines in Tc1 and Ts1Rhr mouse cortex]
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[thumbnail of TIFF Figure 5. Dendritic spine classification by morphology, in Tc1 and Ts1Rhr mouse cortex]
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Abstract

Down Syndrome (DS) is a highly prevalent developmental disorder, affecting 1/700 births. Intellectual disability, which affects learning and memory, is present in all cases and is reflected by below average IQ. We sought to determine whether defective morphology and connectivity in neurons of the cerebral cortex may underlie the cognitive deficits that have been described in two mouse models of DS, the Tc1 and Ts1Rhr mouse lines. We utilised in utero electroporation to label a cohort of future upper layer projection neurons in the cerebral cortex of developing mouse embryos with GFP, and then examined neuronal positioning and morphology in early adulthood, which revealed no alterations in cortical layer position or morphology in either Tc1 or Ts1Rhr mouse cortex. The number of dendrites, as well as dendrite length and branching was normal in both DS models, compared with wildtype controls. The sites of projection neuron synaptic inputs, dendritic spines, were analysed in Tc1 and Ts1Rhr cortex at three weeks and three months after birth, and significant changes in spine morphology were observed in both mouse lines. Ts1Rhr mice had significantly fewer thin spines at three weeks of age. At three months of age Tc1 mice had significantly fewer mushroom spines - the morphology associated with established synaptic inputs and learning and memory. The decrease in mushroom spines was accompanied by a significant increase in the number of stubby spines. This data suggests that dendritic spine abnormalities may be a more important contributor to cognitive deficits in DS models, rather than overall neuronal architecture defects.

Type: Article
Title: Alterations to Dendritic Spine Morphology, but Not Dendrite Patterning, of Cortical Projection Neurons in Tc1 and Ts1Rhr Mouse Models of Down Syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0078561
Publisher version: http://dx.doi.org/10.1371/journal.pone.0078561
Language: English
Additional information: PubMed ID: 24205261 © 2013 Haas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1421006
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