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Published Online: 1 April 2022

Transforming Discoveries About Cortical Microcircuits and Gamma Oscillations Into New Treatments for Cognitive Deficits in Schizophrenia

Publication: American Journal of Psychiatry

Abstract

The major cause of disability in schizophrenia is cognitive impairment, which remains largely refractory to existing treatments. This reflects the fact that antipsychotics and other therapies have not been designed to address specific brain abnormalities that cause cognitive impairment. This overview proposes that understanding how specific cellular and synaptic loci within cortical microcircuits contribute to cortical gamma oscillations may reveal treatments for cognitive impairment. Gamma oscillations are rhythmic patterns of high frequency (∼30–100 Hz) neuronal activity that are synchronized within and across brain regions, generated by a class of inhibitory interneurons that express parvalbumin, and recruited during a variety of cognitive tasks. In schizophrenia, both parvalbumin interneuron function and task-evoked gamma oscillations are deficient. While it has long been controversial whether gamma oscillations are merely a biomarker of circuit function or actually contribute to information processing by neuronal networks, recent neurobiological studies in mice have shown that disrupting or enhancing synchronized gamma oscillations can reproduce or ameliorate cognitive deficits resembling those seen in schizophrenia. In fact, transiently enhancing the synchrony of parvalbumin interneuron–generated gamma oscillations can lead to long-lasting improvements in cognition in mice that model aspects of schizophrenia. Gamma oscillations emerge from specific patterns of connections between a variety of cell types within cortical microcircuits. Thus, a critical next step is to understand how specific cell types and synapses generate gamma oscillations, mediate the effects of gamma oscillations on information processing, and/or undergo plasticity following the induction of gamma oscillations. Modulating these circuit loci, potentially in combination with other approaches such as cognitive training and brain stimulation, may yield potent and selective interventions for enhancing cognition in schizophrenia.

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Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 267 - 276
PubMed: 35360913

History

Accepted: 15 February 2022
Published online: 1 April 2022
Published in print: April 2022

Keywords

  1. Schizophrenia Spectrum and Other Psychotic Disorders
  2. Neurocircuitry

Authors

Details

Vikaas S. Sohal, M.D., Ph.D. [email protected]
Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, and Kavli Institute for Fundamental Neuroscience, University of California, San Francisco.

Notes

Send correspondence to Dr. Sohal ([email protected]).

Competing Interests

The author reports no financial relationships with commercial interests.

Funding Information

Supported by NIH grants R01NS116594 and R01MH121342.

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