The Open UniversitySkip to content
 

Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome

Witton, Jonathan; Padmashri, Ragunathan; Zinyuk, Larissa E.; Popov, Victor I.; Kraev, Igor; Line, Samantha J.; Jensen, Thomas P.; Tedoldi, Angelo; Cummings, Damian M.; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Bannerman, David M.; Randall, Andrew D.; Brown, Jonathan T.; Edwards, Frances A.; Rusakov, Dmitri A.; Stewart, Michael G. and Jones, Matt W. (2015). Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome. Nature Neuroscience, 18 pp. 1291–1298.

DOI (Digital Object Identifier) Link: https://doi.org/10.1038/nn.4072
Google Scholar: Look up in Google Scholar

Abstract

Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome, yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here we report dysfunctional connectivity between dentate gyrus and CA3 networks in the transchromosomic Tc1 mouse model of Down syndrome, demonstrating that ultrastructural abnormalities and impaired short-term plasticity at dentate gyrus–CA3 excitatory synapses culminate in impaired coding of new spatial information in CA3 and CA1 and disrupted behavior in vivo. These results highlight the vulnerability of dentate gyrus–CA3 networks to aberrant human chromosome 21 gene expression and delineate hippocampal circuit abnormalities likely to contribute to distinct cognitive phenotypes in Down syndrome.

Item Type: Journal Item
Copyright Holders: 2015 Nature Publishing Group
ISSN: 1546-1726
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot Set Wellcome Trust
Principal FellowshipNot Set Wellcome Trust
Not SetNot SetUK Medical Research Council
Industrial Collaborative StudentshipNot SetUK Medical Research Council
Not SetNot SetBiotechnology and Biological Sciences Research Council
Not SetNot SetEuropean Research Council
Not SetNot SetEuropean Union
FP7 ITN Extrabrain15-14-30000 Russian Science Foundation
Not Set08-04-00049aRussian Foundation
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Centre for Research in Computing (CRC)
Item ID: 43947
Depositing User: Michael Stewart
Date Deposited: 12 Aug 2015 15:47
Last Modified: 04 Oct 2016 11:48
URI: http://oro.open.ac.uk/id/eprint/43947
Share this page:

Altmetrics

Actions (login may be required)

Policies | Disclaimer

© The Open University   + 44 (0)870 333 4340   general-enquiries@open.ac.uk