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Publication : Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome.

First Author  Witton J Year  2015
Journal  Nat Neurosci Volume  18
Issue  9 Pages  1291-1298
PubMed ID  26237367 Mgi Jnum  J:225795
Mgi Id  MGI:5694508 Doi  10.1038/nn.4072
Citation  Witton J, et al. (2015) Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome. Nat Neurosci 18(9):1291-8
abstractText  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.
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