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Neocortical excitation/inhibition balance in information processing and social dysfunction

机译:信息处理和社交功能障碍中的新皮层兴奋/抑制平衡

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摘要

Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
机译:据推测,自闭症和精神分裂症等精神疾病的严重行为缺陷是由神经微电路内兴奋和抑制的细胞平衡(E / I平衡)升高引起的。该假设可以统一病理生理学和遗传学证据的多种来源,但并不易于直接测试。在这里,我们设计和使用几种新颖的光遗传学工具,以因果关系研究自由移动的哺乳动物中的细胞E / I平衡假说,并探索相关的电路生理。小鼠内侧前额叶皮层内细胞E / I平衡的升高而不是降低会引起细胞信息处理的严重损害,这与特定的行为损害和30-80 Hz范围内的高频功率增加有关,两者均已在人类的临床条件下观察到。与E / I平衡假设一致,抑制性细胞兴奋性的补偿性升高部分挽救了E / I平衡升高引起的社会缺陷。这些结果为严重的神经精神疾病相关症状的细胞E / I平衡假说升高提供了支持。

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  • 来源
    《Nature》 |2011年第7363期|p.171-178|共8页
  • 作者单位

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100,Israel;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA Neuroscience Program, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA;

    Institute of Biology, Experimental Biophysics, Humboldt-Universitat,InvalidenstraBe 42, D-10115 Berlin, Germany;

    Institute of Biology, Experimental Biophysics, Humboldt-Universitat,InvalidenstraBe 42, D-10115 Berlin, Germany;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA Neuroscience Program, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA Department of Psychiatry, University of California, San Francisco, San Francisco, California 94143, USA;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA;

    Department of Neurology and Neurological Science, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA;

    Institute of Biology, Experimental Biophysics, Humboldt-Universitat,InvalidenstraBe 42, D-10115 Berlin, Germany;

    Institute of Biology, Experimental Biophysics, Humboldt-Universitat,InvalidenstraBe 42, D-10115 Berlin, Germany;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA;

    Department of Neurology and Neurological Science, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA;

    Institute of Biology, Experimental Biophysics, Humboldt-Universitat,InvalidenstraBe 42, D-10115 Berlin, Germany;

    Department of Bioengineering, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California USA Howard Hughes Medical Institute, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA Department of Psychiatry and Behavioral Sciences, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA CNC Program, W083 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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