Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/nn.4072

Type

Journal article

Journal

Nat Neurosci

Publication Date

09/2015

Volume

18

Pages

1291 - 1298

Keywords

Animals, CA3 Region, Hippocampal, Chromosomes, Human, Pair 21, Dentate Gyrus, Disease Models, Animal, Down Syndrome, Humans, Male, Maze Learning, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Nerve Net, Organ Culture Techniques, Trisomy