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Dp(10)2Yey mouse model of Down syndrome exhibits aberrant cognition, hippocampal-prefrontal neural dynamics and cytoarchitecture

ABSTRACT: The Dp(10)2Yey mouse carries a ~2.3 Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that makes it an essential model for aspects of Down syndrome (DS, trisomy 21). Specifically, these animals carry extra copies of Mmu10 genes that are homologous to those on human chromosome 21 (Hsa21). Here, we report spatial memory impairment and anxiety-like behaviour in this model alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey DS mice showed impaired spatial alternation associated with increased ripple activity in mPFC during the 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE214273 | GEO | 2023/02/22

REPOSITORIES: GEO

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Chr21 protein-protein interactions: enrichment in proteins involved in intellectual disability, autism and late-onset Alzheimer’s disease

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