ArticleMolecular psychiatry2015
Inhibition of parvalbumin-expressing interneurons results in complex behavioral changes.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 107 citations in OpenAlex.
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- Disorganized Inhibitory Dynamics in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice.bioRxiv : the preprint server for biology · 2026Article
- An ace in the hole? Opportunities and limits of using mice to understand schizophrenia neurobiology.Molecular psychiatry · 2025Review
- Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.Schizophrenia bulletin · 2024Article
- Sex-Specific Impacts of Early Life Sleep Disruption: Ethanol Seeking, Social Interaction, and Anxiety Are Differentially Altered in Adolescent Prairie Voles.Developmental psychobiology · 2024Article
- Timed fetal inflammation and postnatal hypoxia cause cortical white matter injury, interneuron imbalances, and behavioral deficits in a double-hit rat model of encephalopathy of prematurity.Brain, behavior, & immunity - health · 2024Article
- Intracellular spatial transcriptomic analysis toolkit (InSTAnT).Nature communications · 2024Article
- Pyramidal and parvalbumin neurons modulate the process of electroacupuncture stimulation for stroke rehabilitation.iScience · 2024Article
- Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction.Clinical EEG and neuroscience · 2024Article
- GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.Frontiers in cellular neuroscience · 2024Review
- Temperament Traits in Pediatric Obsessive-Compulsive Disorder in Relation to Tourette Syndrome and Attention-Deficit Hyperactivity Disorder.Psychopathology · 2024Article
- Serine racemase deletion alters adolescent social behavior and whole-brain cFos activation.Frontiers in psychiatry · 2024Article
- 16p11.2 deletion mice exhibit compromised fronto-temporal connectivity, GABAergic dysfunction, and enhanced attentional ability.Communications biology · 2023Article
- microRNA-dependent regulation of gene expression in GABAergic interneurons.Frontiers in cellular neuroscience · 2023Review
- Beyond the γ-aminobutyric acid hypothesis of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Parvalbumin interneuron-derived tissue-type plasminogen activator shapes perineuronal net structure.BMC biology · 2022Article
- Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice.Nature communications · 2022Article
- Age- and sex-specific effects of stress on parvalbumin interneurons in preclinical models: Relevance to sex differences in clinical neuropsychiatric and neurodevelopmental disorders.Neuroscience and biobehavioral reviews · 2021Review
- Non-cell-autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse.Molecular psychiatry · 2021Article
- Chemogenetic Activation of Cortical Parvalbumin-Positive Interneurons Reverses Noise-Induced Impairments in Gap Detection.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Reduced expression of the Gad1 gene-encoded 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of schizophrenia. GAD67 downregulation occurs in multiple interneuronal sub-populations, including the parvalbumin-positive (PVALB+) cells. To investigate the role of the PV-positive GABAergic interneurons in behavioral and molecular processes, we knocked down the Gad1 transcript using a microRNA engineered to target specifically Gad1 mRNA under the control of Pvalb bacterial artificial chromosome. Verification of construct expression was performed by immunohistochemistry. Follow-up electrophysiological studies revealed a significant reduction in γ-aminobutyric acid (GABA) release probability without alterations in postsynaptic membrane properties or changes in glutamatergic release probability in the prefrontal cortex pyramidal neurons. Behavioral characterization of our transgenic (Tg) mice uncovered that the Pvalb/Gad1 Tg mice have pronounced sensorimotor gating deficits, increased novelty-seeking and reduced fear extinction. Furthermore, NMDA (N-methyl-d-aspartate) receptor antagonism by ketamine had an opposing dose-dependent effect, suggesting that the differential dosage of ketamine might have divergent effects on behavioral processes. All behavioral studies were validated using a second cohort of animals. Our results suggest that reduction of GABAergic transmission from PVALB+ interneurons primarily impacts behavioral domains related to fear and novelty seeking and that these alterations might be related to the behavioral phenotype observed in schizophrenia.
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