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Alterations in cortical interneurons and cognitive function in schizophrenia.

Samuel J Dienel1, David A Lewis2

  • 1Medical Scientist Training Program, University of Pittsburgh, United States; Translational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pittsburgh, United States.

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Schizophrenia involves working memory deficits linked to altered brain activity. This review highlights how impaired GABA signaling in the prefrontal cortex disrupts gamma oscillations and working memory, contributing to schizophrenia symptoms.

Keywords:
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Area of Science:

  • Neuroscience
  • Psychiatry
  • Molecular Biology

Background:

  • Schizophrenia is associated with working memory deficits, potentially linked to prefrontal cortex (PFC) gamma oscillations.
  • Gamma oscillations and working memory rely on GABA neurotransmission, making it a key area of study in schizophrenia.

Purpose of the Study:

  • To review in vivo and postmortem studies examining GABAergic signaling, gamma oscillations, and working memory in schizophrenia.
  • To elucidate the cellular and molecular underpinnings of these disturbances in the PFC and other cortical regions.

Main Methods:

  • Review of in vivo neuroimaging studies linking GABA markers to gamma oscillations and working memory.
  • Analysis of postmortem studies providing molecular and cellular insights into GABA neurotransmission.

Main Results:

  • Inhibitory GABA signaling, particularly involving parvalbumin-positive basket cells and pyramidal cells in the PFC, is crucial for gamma oscillations and working memory.
  • Disruptions in this specific GABAergic signaling pathway are implicated in the altered gamma oscillations and impaired working memory observed in schizophrenia.

Conclusions:

  • Impaired GABAergic signaling in the PFC is a significant factor contributing to working memory deficits and altered gamma oscillations in schizophrenia.
  • Abnormalities in GABAergic systems extend beyond the PFC to other cortical regions involved in working memory networks.