ArticleFrontiers in cellular neuroscience2013
Paradoxical proepileptic response to NMDA receptor blockade linked to cortical interneuron defect in stargazer mice.
Article in Frontiers in cellular neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Convergent Inhibitory Cortical Circuit Disruption Drives Genetically Distinct Absence Seizures.bioRxiv : the preprint server for biology · 2026Article
- Parvalbumin interneuron activation rescues both seizures and impaired social novelty in digenic absence epilepsy mice.Science advances · 2026Article
- Molecular Basis of GABA Aminotransferase Inhibition in Epilepsy: Structure, Mechanisms, and Drug Development.Current issues in molecular biology · 2025Review
- Parvalbumin Interneuron Dysfunction in Neurological Disorders: Focus on Epilepsy and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Microcircuit failure in STXBP1 encephalopathy leads to hyperexcitability.Cell reports. Medicine · 2023Article
- Targeting NMDA Receptor Complex in Management of Epilepsy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Removal of KCNQ2 from parvalbumin-expressing interneurons improves anti-seizure efficacy of retigabine.Experimental neurology · 2022Article
- Home-cage behavior in the Stargazer mutant mouse.Scientific reports · 2022Article
- Chronic partial TrkB activation reduces seizures and mortality in a mouse model of Dravet syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention.Frontiers in integrative neuroscience · 2022Review
- The Impact of Glutamatergic Synapse Dysfunction in the Corticothalamocortical Network on Absence Seizure Generation.Frontiers in molecular neuroscience · 2022Review
- Impact of Dysfunctional Feed-Forward Inhibition on Glutamate Decarboxylase Isoforms and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
- Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation.Metabolic brain disease · 2021Article
- The Critical Modulatory Role of Spiny Stellate Cells in Seizure Onset Based on Dynamic Analysis of a Neural Mass Model.Frontiers in neuroscience · 2021Article
- Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures.Frontiers in cellular neuroscience · 2021Article
- Developmental changes of GABA immunoreactivity in cortico-thalamic networks of an absence seizure model.Neuropharmacology · 2018Article
- Asynchronous suppression of visual cortex during absence seizures in stargazer mice.Nature communications · 2018Article
- Persistent aberrant cortical phase-amplitude coupling following seizure treatment in absence epilepsy models.The Journal of physiology · 2017Article
- Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder.Molecular psychiatry · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Paradoxical seizure exacerbation by anti-epileptic medication is a well-known clinical phenomenon in epilepsy, but the cellular mechanisms remain unclear. One possibility is enhanced network disinhibition by unintended suppression of inhibitory interneurons. We investigated this hypothesis in the stargazer mouse model of absence epilepsy, which bears a mutation in stargazin, an AMPA receptor trafficking protein. If AMPA signaling onto inhibitory GABAergic neurons is impaired, their activation by glutamate depends critically upon NMDA receptors. Indeed, we find that stargazer seizures are exacerbated by NMDA receptor blockade with CPP (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid) and MK-801, whereas other genetic absence epilepsy models are sensitive to these antagonists. To determine how an AMPA receptor trafficking defect could lead to paradoxical network activation, we analyzed stargazin and AMPA receptor localization and found that stargazin is detected exclusively in parvalbumin-positive (PV (+)) fast-spiking interneurons in somatosensory cortex, where it is co-expressed with the AMPA receptor subunit GluA4. PV (+) cortical interneurons in stargazer show a near twofold decrease in the dendrite:soma GluA4 expression ratio compared to wild-type (WT) littermates. We explored the functional consequence of this trafficking defect on network excitability in neocortical slices. Both NMDA receptor antagonists suppressed 0 Mg (2) (+)-induced network discharges in WT but augmented bursting in stargazer cortex. Interneurons mediate this paradoxical response, since the difference between genotypes was masked by GABA receptor blockade. Our findings provide a cellular locus for AMPA receptor-dependent signaling defects in stargazer cortex and define an interneuron-dependent mechanism for paradoxical seizure exacerbation in absence epilepsy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.