title: Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia.
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.
authors.affiliation: Department of Psychiatry, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Hoftman
authors.affiliation: Department of Psychiatry, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Dibyadeep
authors.initials: D
authors.lastname: Datta
authors.affiliation: 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: lewisda@upmc.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D006801:Humans; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons; D017397:Prefrontal Cortex / Q000473:pathology* / Q000503:physiopathology; D012559:Schizophrenia / Q000473:pathology*
keywords: Cortical development; Dorsolateral prefrontal cortex; Excitation/inhibition balance; Parvalbumin interneurons; Pyramidal cells; Schizophrenia