Cited by 147Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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

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Glausier, J R, Fish, K N, Lewis, D A·2014·Molecular Psychiatry

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 GABA(A) 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 GABA(A) 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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Authors
Glausier, J. R., Fish, K. N., & Lewis, D. A.
Affiliations
University of Pittsburgh (US)
Corresponding author
Lewis, D A
Venue
Molecular Psychiatry
Published
2013-11-12
Volume
19
Issue
1
Pages
30-36
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2081720232
Cited by
147
References
52
Citations by year
2026: 6 · 2025: 9 · 2024: 11 · 2023: 5 · 2022: 9 · 2021: 16 · 2020: 9 · 2019: 10 · 2018: 15 · 2017: 7 · 2016: 19 · 2015: 18 · 2014: 11 · 2013: 1
FWCI
11.56
Type
journal article
Language
en
Update notices
erratum (2013-12-03)
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (P50MH084053, MH084053, R01MH043784, R01MH096985, R01MH071533, MH088160, MH096985, F32MH088160, MH043784)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
schizophrenia, parvalbumin basket cells, dorsolateral prefrontal cortex, GABAergic interneurons, GABA-A receptor alpha1 subunit, GAD65, synaptic input, postmortem brain
MeSH terms
Adult, Aged, Female, Glutamate Decarboxylase, Humans, Male, Middle Aged, Nerve Net, Neurons, Parvalbumins, Receptors, GABA-A, Schizophrenia, Case-Control Studies, Prefrontal Cortex, Presynaptic Terminals

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