Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome
Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome
复制标题
DOI：
10.1016/j.celrep.2019.12.065
复制
发表时间：
2020-01-28
期刊：
影响因子：
8.8
通讯作者：
Fisher, Elizabeth M. C.
中科院分区：
文献类型：
--
作者：
Chang, Pishan;Bush, Daniel;Fisher, Elizabeth M. C.
内侧前额叶皮层（mPFC）和海马的神经动力学改变可能导致复杂染色体疾病唐氏综合征（DS）的认知障碍。在这里，我们证明了非重叠的行为差异与海马和mPFC电生理学的明显异常，在一个典型的空间工作记忆任务中的三个部分三体小鼠模型DS（Dp 1 Tyb，Dp 10 Yey和Dp 17 Yey），共同涵盖了所有区域的同源性与人类21号染色体（Hsa 21）。Dp 1 Tyb小鼠的决策速度较慢（与DYRK 1A的基因剂量无关，DYRK 1A与DS认知功能障碍有关）和θ动力学改变（频率降低，海马-mPFC相干性增加，海马高γ的调节增加）; Dp 10 Yey小鼠显示交替性能受损和海马低γ的θ调节降低;和Dp 17 Yey小鼠与野生型没有显著差异。这些结果将特定的海马和mPFC电路功能障碍与DS模型中的认知缺陷联系起来，重要的是，将它们映射到Hsa 21的离散区域。
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.