A Loss of Parvalbumin-Containing Interneurons Is Associated with Diminished Oscillatory Activity in an Animal Model of Schizophrenia
Open accessAbstract
Decreased GABAergic signaling is among the more robust pathologies observed postmortem in schizophrenia; however, the functional consequences of this deficit are still largely unknown. Here, we demonstrate, in a verified animal model of schizophrenia, that a reduced expression of parvalbumin (PV)-containing interneurons is correlated with a reduction in coordinated neuronal activity during task performance in freely moving rats. More specifically, methylazoxymethanol acetate (MAM)-treated rats display a decreased density of parvalbumin-positive interneurons throughout the medial prefrontal cortex (mPFC) and ventral (but not dorsal) subiculum of the hippocampus. Furthermore, the reduction in interneuron functionality is correlated with a significantly reduced gamma-band response to a conditioned tone during a latent inhibition paradigm. Finally, deficits in mPFC and ventral hippocampal oscillatory activity are associated with an impaired behavioral expression of latent inhibition in MAM-treated rats. Thus, we propose that a decrease in intrinsic GABAergic signaling may be responsible, at least in part, for the prefrontal and hippocampal hypofunctionality observed during task performance, which is consistently observed in animal models as well as in schizophrenia in humans. In addition, a deficit in intrinsic GABAergic signaling may be the origin of the hippocampal hyperactivity purported to underlie the dopamine dysfunction in psychosis. Such information is central to gaining a better understanding of the disease pathophysiology and alternate pharmacotherapeutic approaches.
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Animal models that mimic schizophrenia reproduce the loss of PV-INs in the hippocampus.
“Animal models that mimic schizophrenia replicate the loss of PV-INs in the hippocampus [6,14,15], and show a loss of PV fluorescence per cell in prelimbic regions [16].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [6]
In the MAM model of schizophrenia, reduced PV-IN expression correlates with reduced coordinated neuronal activity during task performance in rats.
“In the MAM model of schizophrenia, reduced expression of PV-INs has been correlated with a reduction in coordinated neuronal activity during task performance in rats [6].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [6]
The prenatal administration of MAM yields adult rats with fewer interneurons expressing PV and loss of high-frequency oscillations.
“the prenatal administration of MAM yields adult rats with fewer interneurons expressing PV and loss of high-frequency oscillations.38”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [38]
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- Authors
- Lodge, D. J., Behrens, M. M., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- University of California San Diego (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-02-25
- Volume
- 29
- Issue
- 8
- Pages
- 2344-2354
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2754752
- OpenAlex
- W2098205950
- Cited by
- 488
- References
- 64
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 20 · 2023: 27 · 2022: 28 · 2021: 43 · 2020: 27 · 2019: 24 · 2018: 31 · 2017: 17 · 2016: 30 · 2015: 37 · 2014: 36 · 2013: 30 · 2012: 26
- FWCI
- 22.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (2r01mh057440-26a1)
- U.S. Public Health Service (MH57440)
- National Institute of Mental Health (MH-57440, R01-MH057440, R37MH057440)
- 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 interneurons, GABAergic neurotransmission, medial prefrontal cortex, ventral hippocampus, gamma oscillations, latent inhibition, hippocampal hyperactivity, dopaminergic dysfunction, animal models of schizophrenia
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Biological Clocks, Conditioning, Psychological, Disease Models, Animal, Electroencephalography, Evoked Potentials, Fear, Female, Glutamate Decarboxylase, Hippocampus, Interneurons, Male, Methylazoxymethanol Acetate, Neural Inhibition, Neurotoxins, Parvalbumins, Pregnancy, Schizophrenia, Spectrum Analysis, Prefrontal Cortex, Rats
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.
Statistics and arithmetic are recomputed, not judged.
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