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Neocortical excitation/inhibition balance in information processing and social dysfunction.

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.

Pubmed ID: 21796121


  • Yizhar O
  • Fenno LE
  • Prigge M
  • Schneider F
  • Davidson TJ
  • O'Shea DJ
  • Sohal VS
  • Goshen I
  • Finkelstein J
  • Paz JT
  • Stehfest K
  • Fudim R
  • Ramakrishnan C
  • Huguenard JR
  • Hegemann P
  • Deisseroth K



Publication Data

September 8, 2011

Associated Grants

  • Agency: NIH HHS, Id: DP1 OD000616
  • Agency: NIMH NIH HHS, Id: R01 MH075957
  • Agency: NIMH NIH HHS, Id: R01 MH086373
  • Agency: NINDS NIH HHS, Id: R01 NS006477
  • Agency: NINDS NIH HHS, Id: R01 NS034774
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Autistic Disorder
  • Disease Models, Animal
  • HEK293 Cells
  • Hippocampus
  • Humans
  • Learning
  • Mental Disorders
  • Mice
  • Models, Neurological
  • Motor Activity
  • Neural Inhibition
  • Neurons
  • Opsins
  • Prefrontal Cortex
  • Schizophrenia
  • Social Behavior