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

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 alter-ations 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.

Automated summary

The Dp(10)2Yey mouse, carrying a -2.3-Mb intra-chromosomal duplication of mouse chromosome 10 that is homologous to human chromosome 21, serves as a crucial model for studying Down syndrome. This study examined the neuronal dysfunction in these mice and found spatial memory impairment and anxiety-like behavior, along with altered neural activity in the medial prefrontal cortex and hippocampus. Additionally, alterations in interneuron subtypes were observed, suggesting potential approaches for ameliorating the effects of trisomy 21.