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Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia.

Authors
  • Hoftman, Gil D1
  • Datta, Dibyadeep1
  • Lewis, David A2
  • 1 Department of Psychiatry, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 2 Department of Psychiatry, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; School of Medicine, and the Department of Neuroscience, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: [email protected].
Type
Published Article
Publication Date
May 15, 2017
Volume
81
Issue
10
Pages
862–873
Identifiers
DOI: 10.1016/j.biopsych.2016.05.022
PMID: 27455897
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Convergent evidence suggests that schizophrenia is a disorder of neurodevelopment with alterations in both early and late developmental processes hypothesized to contribute to the disease process. Abnormalities in certain clinical features of schizophrenia, such as working memory impairments, depend on distributed neural circuitry including the dorsolateral prefrontal cortex (DLPFC) and appear to arise during the protracted maturation of this circuitry across childhood and adolescence. In particular, the neural circuitry substrate for working memory in primates involves the coordinated activity of excitatory pyramidal neurons and a specific population of inhibitory gamma-aminobutyric acid neurons (i.e., parvalbumin-containing basket cells) in layer 3 of the DLPFC. Understanding the relationships between the normal development of-and the schizophrenia-associated alterations in-the DLPFC circuitry that subserves working memory could provide new insights into the nature of schizophrenia as a neurodevelopmental disorder. Consequently, we review the following in this article: 1) recent findings regarding alterations of DLPFC layer 3 circuitry in schizophrenia, 2) the developmental refinements in this circuitry that occur during the period when the working memory alterations in schizophrenia appear to arise and progress, and 3) how various adverse environmental exposures could contribute to developmental disturbances of this circuitry in individuals with schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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