Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

Chang, Pishan; Bush, Daniel; Schorge, Stephanie; Good, Mark; Canonica, Tara; Shing, Nathanael; Noy, Suzanna; Wiseman, Frances K.; Burgess, Neil; Tybulewicz, Victor L.J.; Walker, Matthew C.; Fisher, Elizabeth M.C.

doi:10.1016/j.celrep.2019.12.065

Cited by 47Down syndrome and intellectual disability researchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

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Chang, Pishan, Bush, Daniel, Schorge, Stephanie, Good, Mark, Canonica, Tara, Shing, Nathanael, Noy, Suzanna, Wiseman, Frances K. +4 more·2020·Cell Reports

DOI 10.1016/j.celrep.2019.12.065PMC PMC6996020

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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.

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In Down syndrome, particular neurodevelopmental events are delayed in forebrain regions such as neurogenesis, migration and synaptogenesis, eventually resulting in altered prefrontal circuitry.
“Particular neurodevelopmental events are delayed in forebrain regions such as neurogenesis, migration and synaptogenesis eventually resulting in altered prefrontal circuitry [294–296].”
From Development of prefrontal cortex (2022) · cites this paper as [296]
The Introduction and Abstract (page numbers unavailable) describe abnormalities in medial prefrontal function and neural dynamics in Down syndrome models. They do not report delayed neurogenesis, migration, or synaptogenesis in forebrain regions, or establish that those delays cause the altered circuitry. (LLM, conf=0.84)
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Authors: Chang, P., Bush, D., Schorge, S., Good, M., Canonica, T., Shing, N., Noy, S., Wiseman, F. K., Burgess, N., Tybulewicz, V. L. J., Walker, M. C., & Fisher, E. M. C.
Affiliations: UCL Queen Square Institute of Neurology (GB)
Cardiff University (GB)
The Francis Crick Institute (GB)
Corresponding author: Walker, Matthew C.
ORCID: Chang, Pishan
Bush, Daniel
Good, Mark
Canonica, Tara
Shing, Nathanael
Noy, Suzanna
Wiseman, Frances K.
Burgess, Neil
Tybulewicz, Victor L.J.
Walker, Matthew C.
Fisher, Elizabeth M.C.
Venue: Cell Reports
Publisher: Elsevier BV
Published: 2020-01
Volume: 30
Issue: 4
Pages: 1152-1163.e4
ISSN: 2211-1247 (ISSN-L)
DOI: 10.1016/j.celrep.2019.12.065
PMC: PMC6996020
OpenAlex: W3003528882
Cited by: 47
References: 101
Citations by year: 2026: 3 · 2025: 5 · 2024: 9 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 1
FWCI: 5.43
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cell Reports (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
UCL Discovery (University College London) (submittedVersion)
Figshare (submittedVersion, cc-by)
Explore Bristol Research (submittedVersion)
Spiral (Imperial College London) (submittedVersion, cc-by)
The Francis Crick Institute (cc-by)
Funders: Medical Research Council (U117527252)
Francis Crick Institute
Wellcome Trust (098327, 080174, 098328)
Cancer Research UK (FC001194, 202805/Z/16/Z)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: Down syndrome, mouse model, hippocampus, medial prefrontal cortex, neural dynamics, spatial working memory, theta oscillations, gamma oscillations, decision-making, DYRK1A, cognitive impairment
MeSH terms: Dyrk Kinases, Animals, Chromosomes, Human, Pair 21, Disease Models, Animal, Down Syndrome, Electroencephalography, Hippocampus, Humans, Male, Memory, Short-Term, Mice, Inbred C57BL, Protein-Tyrosine Kinases, Theta Rhythm, Trisomy, Protein Serine-Threonine Kinases, Prefrontal Cortex, Mice, Cognitive Dysfunction, Spatial Memory

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Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

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