Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome.
Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome.
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DOI：
10.1038/nn.4072
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发表时间：
2015-09
影响因子：
25
通讯作者：
Jones MW
中科院分区：
文献类型：
--
作者：
Witton J;Padmashri R;Zinyuk LE;Popov VI;Kraev I;Line SJ;Jensen TP;Tedoldi A;Cummings DM;Tybulewicz VLJ;Fisher EMC;Bannerman DM;Randall AD;Brown JT;Edwards FA;Rusakov DA;Stewart MG;Jones MW
海马神经病理学可能导致唐氏综合征（DS）的认知障碍，但这种病理学的神经网络基础及其对认知障碍不同方面的贡献仍不清楚。在这里，我们报告功能障碍的连接齿状回（DG）和CA 3网络之间的transchromosomic Tc 1小鼠模型的DS，表明超微结构异常和受损的短期可塑性在DG-CA 3兴奋性突触最终受损的编码新的空间信息在CA 3和CA 1和破坏的行为在体内。这些结果突出了DG-CA 3网络对人类21号染色体基因表达异常的脆弱性，并描绘了可能导致DS中不同认知表型的海马回路异常。
Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome (DS), yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here, we report dysfunctional connectivity between dentate gyrus (DG) and CA3 networks in the transchromosomic Tc1 mouse model of DS, demonstrating that ultrastructural abnormalities and impaired short-term plasticity at DG-CA3 excitatory synapses culminate in impaired coding of novel spatial information in CA3 and CA1 and disrupted behaviour in vivo. These results highlight the vulnerability of DG-CA3 networks to aberrant human chromosome 21 gene expression, and delineate hippocampal circuit abnormalities likely to contribute to distinct cognitive phenotypes in DS.