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

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Title: Altered hippocampal-prefrontal neural dynamics in mouse models of down syndrome
Authors: Chang, P
Bush, D
Schorge, S
Good, M
Canonica, T
Shing, N
Noy, S
Wiseman, FK
Burgess, N
Tybulewicz, VLJ
Walker, MC
Fisher, EMC
Item Type: Journal Article
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.
Issue Date: 28-Jan-2020
Date of Acceptance: 17-Dec-2019
URI: http://hdl.handle.net/10044/1/76727
DOI: 10.1016/j.celrep.2019.12.065
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 1152
End Page: 1163.e4
Journal / Book Title: Cell Reports
Volume: 30
Issue: 4
Copyright Statement: © 2019 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Down syndrome
Trisomy 21
executive function
functional connectivity
gamma
hippocampus
memory
prefrontal cortex
theta
Down syndrome
Trisomy 21
executive function
functional connectivity
gamma
hippocampus
memory
prefrontal cortex
theta
0601 Biochemistry and Cell Biology
Publication Status: Published
Conference Place: United States
Open Access location: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996020/
Online Publication Date: 2020-01-28
Appears in Collections:Department of Immunology and Inflammation