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Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome
File(s)
Author(s)
Witton, J
Padmashri, R
Zinyuk, LE
Popov, VI
Kraev, I
Type
Journal Article
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.
Date Issued
2015-09-01
Date Acceptance
2015-06-29
Citation
Nature Neuroscience, 2015, 18 (9), pp.1291-1298
URI
DOI
ISSN
1546-1726
Publisher
Nature Publishing Group
Start Page
1291
End Page
1298
Journal / Book Title
Nature Neuroscience
Volume
18
Issue
9
Copyright Statement
© 2015 Nuature America, Inc. All rights reserved.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/26237367
PII: nn.4072
Subjects
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
SYNAPTIC PLASTICITY
DENTATE GYRUS
TS65DN MOUSE
WORKING-MEMORY
NMDA RECEPTORS
REGION
CA3
ABNORMALITIES
IMPAIRMENT
SEPARATION
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
Dentate Gyrus
Nerve Net
Chromosomes, Human, Pair 21
Animals
Mice, Inbred C57BL
Humans
Mice
Down Syndrome
Disease Models, Animal
Trisomy
Organ Culture Techniques
Maze Learning
Male
CA3 Region, Hippocampal
Mice, 129 Strain
1109 Neurosciences
1701 Psychology
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2015-08-03