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Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects

Molecular Psychiatry volume 19, pages 30–36 (2014)Cite this article

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A Corrigendum to this article was published on 03 December 2013

Abstract

Cortical circuitry dysfunction in schizophrenia has been studied at many different levels of resolution, but not at the most basic unit of network organization—synaptic inputs. Multi-label electron or confocal light microscopy is required to examine specific types of synaptic inputs, and application of these methods to quantitatively study disease-related changes in human postmortem tissue has not been feasible for technical reasons. We recently developed a multi-label confocal light microscopic approach that makes possible the systematic identification and quantification of synaptic inputs, and of the relative levels of proteins localized to these inputs, in human postmortem tissue. We applied this approach to quantify parvalbumin basket cell (PVBC) inputs in area 9 of the dorsolateral prefrontal cortex from schizophrenia and matched comparison subjects. Tissue sections were triple-labeled for the 65 kD isoform of glutamic acid decarboxylase (GAD65), PV and the GABAA receptor α1 subunit. PVBC axonal boutons were defined as PV/GAD65 dual-labeled puncta, and PVBC inputs were defined as a PVBC bouton that overlapped a GABAA receptor α1 subunit punctum. The density of PVBC inputs was unchanged in subjects with schizophrenia, but levels of PV protein were lower in PVBC boutons. In concert with prior reports, these findings indicate that PVBC dysfunction in schizophrenia reflects molecular and not structural alterations in these cells and their axon terminals.

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Acknowledgements

The authors gratefully acknowledge Brad Rocco for his expertise and assistance with image processing, and Wasiq Sheikh for his imaging assistance.

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  1. J R Glausier and K N Fish: Drs Glausier and Fish contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    J R Glausier, K N Fish & D A Lewis

  2. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    D A Lewis

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Correspondence to D A Lewis.

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Competing interests

David A Lewis currently receives investigator-initiated research support from Bristol-Myers Squibb and Pfizer and in 2011–2013 served as a consultant in the areas of target identification and validation and new compound development to Bristol-Myers Squibb and Concert Pharmaceuticals. Drs Glausier and Fish have no conflict of interest.

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Glausier, J., Fish, K. & Lewis, D. Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects. Mol Psychiatry 19, 30–36 (2014). https://doi.org/10.1038/mp.2013.152

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