Cited by 164Neural dynamics and brain functionNeuroscience and Neuropharmacology ResearchSchizophrenia research and treatment

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Downregulation of Parvalbumin at Cortical GABA Synapses Reduces Network Gamma Oscillatory Activity

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Volman, Vladislav, Behrens, M. Margarita, Sejnowski, Terrence J.·2011·The Journal of Neuroscience

DOI 10.1523/jneurosci.3041-11.2011PMC PMC3257321

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Abstract

Postmortem and functional imaging studies of patients with psychiatric disorders, including schizophrenia, are consistent with a dysfunction of interneurons leading to compromised inhibitory control of network activity. Parvalbumin (PV)-expressing, fast-spiking interneurons interacting with pyramidal neurons generate cortical gamma oscillations (30–80 Hz) that synchronize cortical activity during cognitive processing. In postmortem studies of schizophrenia patients, these interneurons show reduced PV and glutamic acid decarboxylase 67 (GAD67), an enzyme that synthesizes GABA, but the consequences of this downregulation are unclear. We developed a biophysically realistic and detailed computational model of a cortical circuit including asynchronous release from GABAergic interneurons to investigate how reductions in PV and GABA affect gamma oscillations induced by sensory stimuli. Networks with reduced GABA were disinhibited and had altered gamma oscillations in response to stimulation; PV-deficient GABA synapses had increased asynchronous release of GABA, which decreased the level of excitation and reduced gamma-band activity. Combined reductions of PV and GABA resulted in a diminished gamma-band oscillatory activity in response to stimuli, similar to that observed in schizophrenia patients. Our results suggest a mechanism by which reduced GAD67 and PV in fast-spiking interneurons may contribute to cortical dysfunction in schizophrenia and related psychiatric disorders.

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Pinto-Duarte, 2010, Neonatal exposure to NMDA receptor antagonists halts the maturation of parvalbumin-positive fast-spiking interneurons, leading to altered network activity in adulthood, Soc Neurosci Abstr, 36, 363

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Authors: Volman, V., Behrens, M. M., & Sejnowski, T. J.
Affiliations: Salk Institute for Biological Studies (US)
ORCID: Behrens, M. Margarita
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2011-12-07
Volume: 31
Issue: 49
Pages: 18137-18148
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.3041-11.2011
PMC: PMC3257321
OpenAlex: W2092726530
Semantic Scholar: 8856dc2fc5afcdd1f2cff5f3097eafc6570f0a07
Cited by: 164
References: 61
Citations by year: 2026: 6 · 2025: 9 · 2024: 6 · 2023: 3 · 2022: 12 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 6 · 2015: 17 · 2014: 19 · 2013: 25 · 2012: 17
FWCI: 9.90
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (0822283)
Howard Hughes Medical Institute
National Institutes of Health (5r01ns059740-04)
University of California, San Diego (PHY-0822283)
National Institute of Mental Health (R01MH091407, MH091407)
National Institute of Neurological Disorders and Stroke (R01-NS-059740, NS059740)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: parvalbumin, fast-spiking interneurons, gamma oscillations, GABAergic synapses, glutamic acid decarboxylase 67, schizophrenia, cortical inhibition, asynchronous neurotransmitter release, computational neural network model
MeSH terms: Action Potentials, Biological Clocks, Cerebral Cortex, Computer Simulation, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Humans, Interneurons, Models, Neurological, Nerve Net, Parvalbumins, Physical Stimulation, Synapses, Down-Regulation, Nonlinear Dynamics

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Downregulation of Parvalbumin at Cortical GABA Synapses Reduces Network Gamma Oscillatory Activity

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