Neocortical excitation/inhibition balance in information processing and social dysfunction.
Neocortical excitation/inhibition balance in information processing and social dysfunction.
复制标题
DOI：
10.1038/nature10360
复制
发表时间：
2011-07-27
期刊：
影响因子：
64.8
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
--
作者：
Yizhar, Ofer;Fenno, Lief E.;Prigge, Matthias;Schneider, Franziska;Davidson, Thomas J.;O'Shea, Daniel J.;Sohal, Vikaas S.;Goshen, Inbal;Finkelstein, Joel;Paz, Jeanne T.;Stehfest, Katja;Fudim, Roman;Ramakrishnan, Charu;Huguenard, John R.;Hegemann, Peter;Deisseroth, Karl
自闭症和精神分裂症等精神疾病的严重行为缺陷被认为是由神经微回路中细胞兴奋和抑制平衡（E/I平衡）的升高引起的。这一假设可以统一不同的病理生理和遗传证据流，但尚未受到直接测试的影响。在这里，我们设计并使用了几种新的光遗传学工具来因果研究自由运动哺乳动物的细胞E/I平衡假说，并探索相关的电路生理学。研究发现，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伤，与特定行为障碍和30-80 Hz范围内高频功率的增加有关，这两种情况都在人类临床条件下观察到。与E/I平衡假说一致，抑制性细胞兴奋性代偿性升高部分地弥补了E/I平衡升高引起的社会缺陷。这些结果为严重神经精神疾病相关症状的细胞E/I平衡升高假说提供了支持。
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.
登录
查看更多内容
影响因子：
4.9
作者：
Gogolla, Nadine;LeBlanc, Jocelyn J.;Quast, Kathleen B.;Sudhof, Thomas C.;Fagiolini, Michela;Hensch, Takao K.
通讯作者：
Hensch, Takao K.
影响因子：
4.2
作者：
Dichter, Gabriel S.;Felder, Jennifer N.;Bodfish, James W.
通讯作者：
Bodfish, James W.
影响因子：
2.9
作者：
Markram, Kamila;Markram, Henry
通讯作者：
Markram, Henry
DOI：
10.1111/j.1469-7610.2009.02153.x
发表时间：
2010-03-01
影响因子：
7.6
作者：
Belmonte, Matthew K.;Gomot, Marie;Baron-Cohen, Simon
通讯作者：
Baron-Cohen, Simon
影响因子：
64.8
作者：
Adamantidis, Antoine R.;Zhang, Feng;De Lecea, Luis
通讯作者：
De Lecea, Luis