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.
| Original language | English |
|---|---|
| Article number | 106073 |
| Journal | iScience |
| Volume | 26 |
| Issue number | 2 |
| Early online date | 28 Jan 2023 |
| DOIs | |
| Publication status | Published - 17 Feb 2023 |
Bibliographical note
Funding Information:E.M.C.F. and V.L.J.T. were supported by grants from the Wellcome Trust (grant numbers 080174, 098327 and 098328). V.L.J.T. was also supported by the Francis Crick Institute, which receives its core funding from the UK Medical Research Council (FC001194), Cancer Research UK (FC001194), and the Wellcome Trust (FC001194). We thank Eugene Yu for Dp(10)2Yey mice. We also thank Amelia Edwards for single-cell library preparation, and the UCL MRC Prion Unit for animal husbandry. This research was funded by the Wellcome Trust. For the purpose of Open Access, the authors have applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission. Conceptualization, P.C. V.L.J.T. M.C.W. and E.M.C.F.; investigation and data curation, P.C. P.M. M.P.-G. I.Z. K.C. M.L.S. and R.A.; software and analytic tools, D.B. and S.J.W; formal analysis, P.C. D.B. P.M. M.P.-G. I.Z. K.C. M.L.S. and R.A.; resources, V.L.J.T. and E.M.C.F.; supervision, M.C.W. and E.M.C.F.; funding acquisition, V.L.J.T. and E.M.C.F.; writing – original draft and visualization, P.C.; all authors contributed to writing – review & editing. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location.
Funding Information:
E.M.C.F. and V.L.J.T. were supported by grants from the Wellcome Trust (grant numbers 080174 , 098327 and 098328 ). V.L.J.T. was also supported by the Francis Crick Institute , which receives its core funding from the UK Medical Research Council ( FC001194 ), Cancer Research UK ( FC001194 ), and the Wellcome Trust ( FC001194 ). We thank Eugene Yu for Dp(10)2Yey mice. We also thank Amelia Edwards for single-cell library preparation, and the UCL MRC Prion Unit for animal husbandry. This research was funded by the Wellcome Trust. For the purpose of Open Access, the authors have applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
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