ArticleProceedings of the National Academy of Sciences of the United States of America2006
Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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98 citing papers in PubMed, 201 citations in OpenAlex.
- SLC35A2 loss-of-function variants affect glycomic signatures, neuronal fate and network dynamics.Brain : a journal of neurology · 2025Article
- Diverse species of animal models in epilepsy research: Progress and perspectives.Zoological research · 2025Review
- Emerging Role of Tripartite Synaptic Transmission in the Pathomechanism of Autosomal-Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Review
- H- and m-channel overexpression promotes seizure-like events by impairing the ability of inhibitory neurons to process correlated inputs.PLoS computational biology · 2025Article
- Tonic-clonic seizures induce hypersomnia and suppress rapid eye movement sleep in mouse models of epilepsy.Sleep advances : a journal of the Sleep Research Society · 2025Article
- Pathogenic genes implicated in sleep-related hypermotor epilepsy: a research progress update.Frontiers in neurology · 2024Review
- Rare variants in GABRG2 associated with sleep-related hypermotor epilepsy.Journal of neurology · 2022Article
- Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model.Brain : a journal of neurology · 2022Article
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- Can rodent models elucidate the pathomechanisms of genetic epilepsy?British journal of pharmacology · 2022Review
- Neuromodulatory control of inhibitory network arborization in the developing postnatal neocortex.Science advances · 2022Article
- Alterations of Neuronal Dynamics as a Mechanism for Cognitive Impairment in Epilepsy.Current topics in behavioral neurosciences · 2022Review
- The Critical Modulatory Role of Spiny Stellate Cells in Seizure Onset Based on Dynamic Analysis of a Neural Mass Model.Frontiers in neuroscience · 2021Article
- Focal corticarl dysplasia in epilepsy is associated with GABA increase.NeuroImage. Clinical · 2021Article
- A Role for Vasoactive Intestinal Peptide Interneurons in Neurodevelopmental Disorders.Developmental neuroscience · 2021Review
- Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology.Brain sciences · 2020Review
- Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.Cell reports · 2020Article
- Neurostimulation stabilizes spiking neural networks by disrupting seizure-like oscillatory transitions.Scientific reports · 2020Article
- Genetics of Epileptic Networks: from Focal to Generalized Genetic Epilepsies.Current neurology and neuroscience reports · 2020Review
- Preclinical insights into therapeutic targeting of KCC2 for disorders of neuronal hyperexcitability.Expert opinion on therapeutic targets · 2020Review
38 more citing papers are in PubMed but not listed here.
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6 authors at 3 institutions in 1 country.
Funding
Abstract
Selected mutations in the human alpha4 or beta2 neuronal nicotinic acetylcholine receptor subunit genes cosegregate with a partial epilepsy syndrome known as autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To examine possible mechanisms underlying this inherited epilepsy, we engineered two ADNFLE mutations (Chrna4(S252F) and Chrna4(+L264)) in mice. Heterozygous ADNFLE mutant mice show persistent, abnormal cortical electroencephalograms with prominent delta and theta frequencies, exhibit frequent spontaneous seizures, and show an increased sensitivity to the proconvulsant action of nicotine. Relative to WT, electrophysiological recordings from ADNFLE mouse layer II/III cortical pyramidal cells reveal a >20-fold increase in nicotine-evoked inhibitory postsynaptic currents with no effect on excitatory postsynaptic currents. i.p. injection of a subthreshold dose of picrotoxin, a use-dependent gamma-aminobutyric acid receptor antagonist, reduces cortical electroencephalogram delta power and transiently inhibits spontaneous seizure activity in ADNFLE mutant mice. Our studies suggest that the mechanism underlying ADNFLE seizures may involve inhibitory synchronization of cortical networks via activation of mutant alpha4-containing nicotinic acetylcholine receptors located on the presynaptic terminals and somatodendritic compartments of cortical GABAergic interneurons.
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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.