Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

Muza, Phillip M., Bush, Daniel, Pérez-González, Marta, Zouhair, Ines, Cleverley, Karen, Sopena, Miriam L., Aoidi, Rifdat, West, Steven J., Good, Mark ORCID: https://orcid.org/0000-0002-1824-1203, Tybulewicz, Victor L.J., Walker, Matthew C., Fisher, Elizabeth M.C. and Chang, Pishan 2023. Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture. iScience 26 (2) , pp. 1-22. 10.1016/j.isci.2023.106073

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Abstract

The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology
Publisher:	Cell Press
ISSN:	2589-0042
Date of First Compliant Deposit:	3 April 2023
Date of Acceptance:	24 January 2023
Last Modified:	26 May 2023 03:36
URI:	https://orca.cardiff.ac.uk/id/eprint/158294

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