Haas, MA; Bell, D; Slender, A; Lana-Elola, E; Watson-Scales, S; Fisher, EMC; Tybulewicz, VLJ; Haas, MA; Bell, D; Slender, A; Lana-Elola, E; Watson-Scales, S; Fisher, EMC; Tybulewicz, VLJ; Guillemot, F; - view fewer (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.

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Preview	Other (TIFF Figure 1. Hsa21, orthologous mouse chromosome regions and relevant DS mouse models) journal.pone.0078561.g001.tif Download (423kB)
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Preview	Other (TIFF Figure 3. Layer II–IV cortical projection neuron morphology in Tc1 and Ts1Rhr mice) journal.pone.0078561.g003.tif Download (1MB)
Preview	Other (TIFF Figure 4. Dendritic spines in Tc1 and Ts1Rhr mouse cortex) journal.pone.0078561.g004.tif Download (1MB)
Preview	Other (TIFF Figure 5. Dendritic spine classification by morphology, in Tc1 and Ts1Rhr mouse cortex) journal.pone.0078561.g005.tif Download (601kB)

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.

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