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Altered hippocampal-prefrontal neural dynamics in mouse models of Down syndrome

Chang, Pishan, Bush, Daniel, Schorge, Stephanie, Good, Mark ORCID: https://orcid.org/0000-0002-1824-1203, Canonica, Tara, Shing, Nathanael, Noy, Suzanna, Wiseman, Frances K., Burgess, Neil, Tybulewicz, Victor L. J., Walker, Matthew C. and Fisher, Elizabeth M. C. 2020. Altered hippocampal-prefrontal neural dynamics in mouse models of Down syndrome. Cell Reports 30 (4) , 1152-1163.e4. 10.1016/j.celrep.2019.12.065

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Abstract

Altered neural dynamics in the medial prefrontal cortex (mPFC) and hippocampus may contribute to cognitive impairments in the complex chromosomal disorder Down syndrome (DS). Here, we demonstrate non-overlapping behavioral differences associated with distinct abnormalities in hippocampal and mPFC electrophysiology during a canonical spatial working memory task in three partially trisomic mouse models of DS (Dp1Tyb, Dp10Yey, and Dp17Yey) that together cover all regions of homology with human chromosome 21 (Hsa21). Dp1Tyb mice show slower decision-making (unrelated to the gene dose of DYRK1A, which has been implicated in DS cognitive dysfunction) and altered theta dynamics (reduced frequency, increased hippocampal-mPFC coherence, and increased modulation of hippocampal high gamma); Dp10Yey mice show impaired alternation performance and reduced theta modulation of hippocampal low gamma; and Dp17Yey mice are not significantly different from the wild type. These results link specific hippocampal and mPFC circuit dysfunctions to cognitive deficits in DS models and, importantly, map them to discrete regions of Hsa21.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Additional Information: This is an open access article under the CC-BY license.
Publisher: Elsevier
ISSN: 2211-1247
Date of First Compliant Deposit: 20 November 2019
Date of Acceptance: 17 December 2019
Last Modified: 05 May 2023 08:03
URI: https://orca.cardiff.ac.uk/id/eprint/126991

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