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Three-dimensional synaptic ultrastructure in the dentate gyrus and hippocampal area CA3 in the Ts65Dn mouse model of down syndrome

Popov, Victor I. ; Kleschevnikov, Alexander M.; Klimenko, Oleg A.; Stewart, Michael G. and Belichenko, Pavel V. (2011). Three-dimensional synaptic ultrastructure in the dentate gyrus and hippocampal area CA3 in the Ts65Dn mouse model of down syndrome. Journal of Comparative Neurology, 519(7) pp. 1338–1354.

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Down syndrome (DS) results from trisomy of human chromosome 21. Ts65Dn mice are an established model for DS and show several phenotypes similar to those in people with DS. However, there is little data on the structural plasticity of synapses in the trisynaptic pathway in the hippocampus. Here we investigate three-dimensional (3D) ultrastructure of synapses in the hippocampus of age-matched control (2N) and Ts65Dn male mice. Serial ultrathin sections and 3D reconstructions characterize synapses in the middle molecular layer (MML) of dentate gyrus and in thorny excrescences (TEs) in proximal portions of apical dendrites of CA3 pyramidal neurons. 3D analysis of synapses shows phenotypes that distinguish Ts65Dn from 2N mice. For the MML, synapse density was reduced by 15% in Ts65Dn vs. 2N mice (P < 0.05). Comparative 3D analyses demonstrate a significant decrease in the number of thorns per TE in CA3 in Ts65Dn vs. 2N mice (by ∼45%, P = 0.01). Individual thorn volume was 3 times smaller in Ts65Dn vs. 2N mice (P = 0.02). A significant decrease in the number of thorn projections per TE in Ts65Dn vs. 2N mice was accompanied by a decrease of filopodium-like protrusions on the surface of TEs (P = 0.02). However, the volume of postsynaptic densities in CA3 Ts65Dn and 2N mice was unchanged (P = 0.78). Our findings suggest that the high degree of plasticity of CA3 thorns may be connected with their filopodial origin. Alterations of 3D synaptic structure in Ts65Dn mice may further contribute to the diminished plasticity in DS.

Item Type: Journal Article
Copyright Holders: 2010 Wiley-Liss, Inc.
ISSN: 1096-9861
Keywords: Down syndrome; Ts65Dn mice; 3D reconstructions; CA3 hippocampal area; dentate gyrus; CA3 thorny excrescences; dendritic spines; postsynaptic densities; filopodia; serial ultrathin sectioning
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 25883
Depositing User: Astrid Peterkin
Date Deposited: 15 Mar 2011 15:38
Last Modified: 24 Feb 2016 07:06
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