Altered parvalbumin basket cell inputs in the dorsolateral prefrontal cortex of schizophrenia subjects
Open accessAbstract
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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Reduced PV expression at individual cellular level and within presynaptic boutons of PV+ basket cells in SZ patients.
“the reduced PV expression is reported both at the individual cellular level 181 and specifically within presynaptic boutons of PV+ basket cells 182.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [182]
No change in density of GABAergic synaptic inputs on DLPFC neurons in SZ patients.
“or the density of GABAergic synaptic inputs on DLPFC neurons 182 is observed in SZ patients”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [182]
Reduced PV and GAD67 protein levels are seen in both prefrontal and temporal cortex of post-mortem brain tissues from schizophrenia patients.
“Reduced PV and GAD67 protein levels are also seen in both prefrontal and temporal cortex of post-mortem brain tissues (Beasley and Reynolds, 1997; Curley et al., 2011; Glausier et al., 2014).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Glausier et al., 2014
Schizophrenia shows less parvalbumin protein in layer 3 parvalbumin basket cell terminals.
“reduced PV protein in PV basket cell terminals in layer 3 (Glausier et al, 2014)”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Glausier et al, 2014
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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
- PMC
- PMC3874728
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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