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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex
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Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex

机译：Dgcr8的缺乏，一个被22q11.2微缺失破坏的基因，导致额叶前皮质的短期可塑性改变

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摘要

Individuals with 22q11.2 microdeletions have cognitive and behavioral impairments and the highest known genetic risk for developing schizophrenia. One gene disrupted by the 22q11.2 micro-deletion is DGCR8, a component of the "microprocessor" complex that is essential for microRNA production, resulting in abnormal processing of specific brain miRNAs and working memory deficits. Here, we determine the effect of Dgcr8 deficiency on the structure and function of cortical circuits by assessing their laminar organization, as well as the neuronal morphology, and intrinsic and syn-aptic properties of layer 5 pyramidal neurons in the prefrontal cortex of Dgcr8~(+/-) mutant mice. We found that heterozygous Dgcr8 mutant mice have slightly fewer cortical layer 2/4 neurons and that the basal dendrites of layer 5 pyramidal neurons have slightly smaller spines. In addition to the modest structural changes, field potential and whole-cell electrophysiological recordings performed in layer 5 of the prefrontal cortex revealed greater short-term synaptic depression during brief stimulation trains applied at 50 Hz to superficial cortical layers. This finding was accompanied by a decrease in the initial phase of synaptic potentiation. Our results identify altered short-term plasticity as a neural substrate underlying the cognitive dysfunction and the increased risk for schizophrenia associated with the 22q11.2 microdeletions.
机译：具有22q11.2微缺失的个体具有认知和行为障碍，并且是发生精神分裂症的已知遗传风险最高。被22q11.2微缺失破坏的一个基因是DGCR8，DGCR8是“微处理器”复合体的一个组成部分，对于产生微小RNA至关重要，它会导致特定大脑miRNA的异常加工和工作记忆缺陷。在这里，我们通过评估Dgcr8缺乏的层状组织，神经元形态以及Dgcr8〜（前额叶皮层中第5层锥体神经元的内在和突触特性）来确定Dgcr8缺乏对皮质回路的结构和功能的影响。 +/-）突变小鼠。我们发现，杂合Dgcr8突变小鼠的皮层2/4神经元略少，而第5层锥体神经元的基底树突具有较小的刺。除了适度的结构变化外，在前额叶皮层的第5层中进行的场电势和全细胞电生理记录还显示，在以50 Hz的频率对浅层皮层施加短时刺激时，短期突触抑制作用更大。这一发现伴随着突触增强初期的减少。我们的研究结果表明，短期可塑性改变是认知功能障碍和22q11.2微缺失导致精神分裂症风险增加的神经底物。

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    Karine Fenelon; Jun Mukai; Bin Xu; Pei-Ken Hsu; Liam J. Drew; Maria Karayiorgou; Gerald D. Fischbach; Amy B. MacDermott; Joseph A. Gogos;

  • 作者单位

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032;

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032;

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032 Department of Psychiatry, Columbia University Medical Center, New York, NY 10032;

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032 Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, New York, NY 10032;

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032;

    Department of Psychiatry, Columbia University Medical Center, New York, NY 10032 New York State Psychiatric Institute, New York, NY 10032;

    Department of Neuroscience, Columbia University Medical Center, New York, NY 10032 The Simons Foundation Autism Research Initiative, New York, NY 10010;

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032 Department of Neuroscience, Columbia University Medical Center, New York, NY 10032;

    Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032 Department of Neuroscience, Columbia University Medical Center, New York, NY 10032;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    22q11.2 deletion syndrome; synaptic plasticity; field EPSP; patch clamp; neurogenesis;

    机译：22q11.2缺失综合征;突触可塑性现场EPSP;膜片夹;神经发生;

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