Author
Listed:
- 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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