The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Medial Prefrontal Cortex in Autism
Open accessAbstract
The cognitive phenotype of autism has been correlated with an altered balance of excitation to inhibition in the cerebral cortex, which could result from a change in the number, function, or morphology of GABA-expressing interneurons. The number of GABAergic interneuron subtypes has not been quantified in the autistic cerebral cortex. We classified interneurons into 3 subpopulations based on expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. We quantified the number of each interneuron subtype in postmortem neocortical tissue from 11 autistic cases and 10 control cases. Prefrontal Brodmann Areas (BA) BA46, BA47, and BA9 in autism and age-matched controls were analyzed by blinded researchers. We show that the number of parvalbumin+ interneurons in these 3 cortical areas-BA46, BA47, and BA9-is significantly reduced in autism compared with controls. The number of calbindin+ and calretinin+ interneurons did not differ in the cortical areas examined. Parvalbumin+ interneurons are fast-spiking cells that synchronize the activity of pyramidal cells through perisomatic and axo-axonic inhibition. The reduced number of parvalbumin+ interneurons could disrupt the balance of excitation/inhibition and alter gamma wave oscillations in the cerebral cortex of autistic subjects. These data will allow development of novel treatments specifically targeting parvalbumin interneurons.
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The number of parvalbumin-immunoreactive interneurons, but not calbindin- or calretinin-expressing ones, is decreased in the medial PFC in ASD, and this decrease is due to fewer chandelier interneurons.
“The number of parvalbumin-immunoreactive interneurons, but not those expressing calbindin or calretinin, is decreased in the medial PFC [148], which was recently confirmed to be due to fewer chandelier interneurons [12].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [148]
PVI circuits are altered in schizophrenia and autism spectrum disorder despite heterogeneity in etiology.
“Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders.”
From Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia (2017) · cites this paper as [9]
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- Authors
- Hashemi, E., Ariza, J., Rogers, H., Noctor, S. C., & Martínez-Cerdeño, V.
- Affiliations
- Shriners Hospitals for Children - Northern California (US)
- University of California Davis Medical Center (US)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-27
- Volume
- 27
- Issue
- 2
- Pages
- bhw021
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC6074948
- OpenAlex
- W2294392975
- Cited by
- 322
- References
- 113
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 32 · 2023: 30 · 2022: 26 · 2021: 49 · 2020: 45 · 2019: 34 · 2018: 30 · 2017: 32 · 2016: 7
- FWCI
- 21.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute for Mental Health (MH094681 and MH101188)
- MIND Institute (U54 HD079125)
- Shriners Hospitals, and the Pathology Department at UCD
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, parvalbumin interneurons, GABAergic interneurons, medial prefrontal cortex, excitation-inhibition balance, interneuron subtypes, calbindin, calretinin, fast-spiking interneurons, gamma oscillations, postmortem brain
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Cell Count, Child, Female, Humans, Interneurons, Male, Middle Aged, Parvalbumins, Calbindins, Calbindin 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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