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Neocortical excitation/inhibition balance in information processing and social dysfunction

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  • Ofer Yizhar

    (W083 Clark Center, 318 Campus Drive West, Stanford University
    Weizmann Institute of Science)

  • Lief E. Fenno

    (W083 Clark Center, 318 Campus Drive West, Stanford University
    Neuroscience Program, W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Matthias Prigge

    (Institute of Biology, Experimental Biophysics, Humboldt-Universität, Invalidenstraße 42)

  • Franziska Schneider

    (Institute of Biology, Experimental Biophysics, Humboldt-Universität, Invalidenstraße 42)

  • Thomas J. Davidson

    (W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Daniel J. O’Shea

    (W083 Clark Center, 318 Campus Drive West, Stanford University
    Neuroscience Program, W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Vikaas S. Sohal

    (W083 Clark Center, 318 Campus Drive West, Stanford University
    University of California, San Francisco)

  • Inbal Goshen

    (W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Joel Finkelstein

    (W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Jeanne T. Paz

    (W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Katja Stehfest

    (Institute of Biology, Experimental Biophysics, Humboldt-Universität, Invalidenstraße 42)

  • Roman Fudim

    (Institute of Biology, Experimental Biophysics, Humboldt-Universität, Invalidenstraße 42)

  • Charu Ramakrishnan

    (W083 Clark Center, 318 Campus Drive West, Stanford University)

  • John R. Huguenard

    (W083 Clark Center, 318 Campus Drive West, Stanford University)

  • Peter Hegemann

    (Institute of Biology, Experimental Biophysics, Humboldt-Universität, Invalidenstraße 42)

  • Karl Deisseroth

    (W083 Clark Center, 318 Campus Drive West, Stanford University
    Howard Hughes Medical Institute, W083 Clark Center, 318 Campus Drive West, Stanford University
    W083 Clark Center, 318 Campus Drive West, Stanford University
    CNC Program, W083 Clark Center, 318 Campus Drive West, Stanford University)

Abstract

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.

Suggested Citation

  • Ofer Yizhar & Lief E. Fenno & Matthias Prigge & Franziska Schneider & Thomas J. Davidson & Daniel J. O’Shea & Vikaas S. Sohal & Inbal Goshen & Joel Finkelstein & Jeanne T. Paz & Katja Stehfest & Roman, 2011. "Neocortical excitation/inhibition balance in information processing and social dysfunction," Nature, Nature, vol. 477(7363), pages 171-178, September.
  • Handle: RePEc:nat:nature:v:477:y:2011:i:7363:d:10.1038_nature10360
    DOI: 10.1038/nature10360
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    Cited by:

    1. Zihao Chen & Yechao Han & Zheng Ma & Xinnian Wang & Surui Xu & Yong Tang & Alexei L. Vyssotski & Bailu Si & Yang Zhan, 2024. "A prefrontal-thalamic circuit encodes social information for social recognition," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Gregory Lepeu & Ellen Maren & Kristina Slabeva & Cecilia Friedrichs-Maeder & Markus Fuchs & Werner J. Z’Graggen & Claudio Pollo & Kaspar A. Schindler & Antoine Adamantidis & Timothée Proix & Maxime O., 2024. "The critical dynamics of hippocampal seizures," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Luye Qin & Jamal B. Williams & Tao Tan & Tiaotiao Liu & Qing Cao & Kaijie Ma & Zhen Yan, 2021. "Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Pan Xu & Yuanlei Yue & Juntao Su & Xiaoqian Sun & Hongfei Du & Zhichao Liu & Rahul Simha & Jianhui Zhou & Chen Zeng & Hui Lu, 2022. "Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Jennifer Isaac & Sonia Corbett Karkare & Hymavathy Balasubramanian & Nicholas Schappaugh & Jarildy Larimar Javier & Maha Rashid & Malavika Murugan, 2024. "Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    6. Lizhu Li & Lihui Lu & Yuqi Ren & Guo Tang & Yu Zhao & Xue Cai & Zhao Shi & He Ding & Changbo Liu & Dali Cheng & Yang Xie & Huachun Wang & Xin Fu & Lan Yin & Minmin Luo & Xing Sheng, 2022. "Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Yu-Jun Wang & Gui-Ying Zan & Cenglin Xu & Xue-Ping Li & Xuelian Shu & Song-Yu Yao & Xiao-Shan Xu & Xiaoyun Qiu & Yexiang Chen & Kai Jin & Qi-Xin Zhou & Jia-Yu Ye & Yi Wang & Lin Xu & Zhong Chen & Jing, 2023. "The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Alexandre Castonguay & Sébastien Thomas & Frédéric Lesage & Christian Casanova, 2014. "Repetitive and Retinotopically Restricted Activation of the Dorsal Lateral Geniculate Nucleus with Optogenetics," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-8, April.
    9. Henry W. Kietzman & Gracy Trinoskey-Rice & Sarah A. Blumenthal & Jidong D. Guo & Shannon L. Gourley, 2022. "Social incentivization of instrumental choice in mice requires amygdala-prelimbic cortex-nucleus accumbens connectivity," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Lloyd E. Russell & Mehmet Fişek & Zidan Yang & Lynn Pei Tan & Adam M. Packer & Henry W. P. Dalgleish & Selmaan N. Chettih & Christopher D. Harvey & Michael Häusser, 2024. "The influence of cortical activity on perception depends on behavioral state and sensory context," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Giulia Faini & Dimitrii Tanese & Clément Molinier & Cécile Telliez & Massilia Hamdani & Francois Blot & Christophe Tourain & Vincent Sars & Filippo Bene & Benoît C. Forget & Emiliano Ronzitti & Valent, 2023. "Ultrafast light targeting for high-throughput precise control of neuronal networks," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Can Tao & Guang-Wei Zhang & Wen-Jian Sun & Junxiang J. Huang & Li I. Zhang & Huizhong Whit Tao, 2024. "Excitation-inhibition imbalance in medial preoptic area circuits underlies chronic stress-induced depression-like states," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    13. Li Ma & Feng Wang & Yangping Li & Jing Wang & Qing Chang & Yuanning Du & Jotham Sadan & Zhen Zhao & Guoping Fan & Bing Yao & Jian-Fu Chen, 2023. "Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Brandon W. Hughes & Jessica L. Huebschman & Evgeny Tsvetkov & Benjamin M. Siemsen & Kirsten K. Snyder & Rose Marie Akiki & Daniel J. Wood & Rachel D. Penrod & Michael D. Scofield & Stefano Berto & Mak, 2024. "NPAS4 supports cocaine-conditioned cues in rodents by controlling the cell type-specific activation balance in the nucleus accumbens," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Noemi S Araújo & Selvin Z Reyes-Garcia & João A F Brogin & Douglas D Bueno & Esper A Cavalheiro & Carla A Scorza & Jean Faber, 2022. "Chaotic and stochastic dynamics of epileptiform-like activities in sclerotic hippocampus resected from patients with pharmacoresistant epilepsy," PLOS Computational Biology, Public Library of Science, vol. 18(4), pages 1-31, April.
    16. Rodrigo G. Fernandez Lahore & Niccolò P. Pampaloni & Enrico Schiewer & M.-Marcel Heim & Linda Tillert & Johannes Vierock & Johannes Oppermann & Jakob Walther & Dietmar Schmitz & David Owald & Andrew J, 2022. "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Qingtao Sun & Jianping Zhang & Anan Li & Mei Yao & Guangcai Liu & Siqi Chen & Yue Luo & Zhi Wang & Hui Gong & Xiangning Li & Qingming Luo, 2022. "Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    18. Weijie Ye & Xiaoying Chen, 2023. "Effects of NMDA Receptor Hypofunction on Inhibitory Control in a Two-Layer Neural Circuit Model," Mathematics, MDPI, vol. 11(19), pages 1-12, September.
    19. Jung Ho Hyun & Kenichiro Nagahama & Ho Namkung & Neymi Mignocchi & Seung-Eon Roh & Patrick Hannan & Sarah Krüssel & Chuljung Kwak & Abigail McElroy & Bian Liu & Mingguang Cui & Seunghwan Lee & Dongmin, 2022. "Tagging active neurons by soma-targeted Cal-Light," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    20. Pfaffelhuber, P. & Rotter, S. & Stiefel, J., 2022. "Mean-field limits for non-linear Hawkes processes with excitation and inhibition," Stochastic Processes and their Applications, Elsevier, vol. 153(C), pages 57-78.

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