ArticleNeurobiology of disease2015
Genetic background modulates impaired excitability of inhibitory neurons in a mouse model of Dravet syndrome.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 103 citations in OpenAlex.
- Translatable electrophysiological and behavioral abnormalities in a humanized model of SYNGAP1-disorder.Molecular psychiatry · 2026Article
- Article
- Urine-Derived iPSC Neurospheres Uncover Proteomic Correlates of Clinical Severity in Dravet Syndrome.Journal of neurochemistry · 2026Article
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- Dravet Syndrome Patient-Derived Neural Cells Present Altered Levels of Potassium, Copper, and Zinc.ACS chemical neuroscience · 2026Article
- Transgenic mouse models of sodium and potassium channelopathies in epilepsy: insights into disease mechanisms and therapeutics.Bioscience reports · 2025Review
- Both GEF domains of the autism and developmental epileptic encephalopathy-associated Trio protein are required for proper tangential migration of GABAergic interneurons.Molecular psychiatry · 2025Article
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
- Fine mapping and candidate gene analysis of Dravet syndrome modifier loci on mouse chromosomes 7 and 8.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.Stem cell reports · 2024Review
- Fine Mapping and Candidate Gene Analysis of Dravet Syndrome Modifier Loci on Mouse Chromosomes 7 and 8.bioRxiv : the preprint server for biology · 2024Article
- Review
- Individualised human phenotype ontology gene panels improve clinical whole exome and genome sequencing analytical efficacy in a cohort of developmental and epileptic encephalopathies.Molecular genetics & genomic medicine · 2023Article
- Viral vector-mediated expression of NaV1.1, after seizure onset, reduces epilepsy in mice with Dravet syndrome.The Journal of clinical investigation · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Acute effect of antiseizure drugs on background oscillations inFrontiers in pharmacology · 2023Article
- Heat-induced seizures, premature mortality, and hyperactivity in a novelFrontiers in cellular neuroscience · 2023Article
- Fine mapping and candidate gene analysis of a dravet syndrome modifier locus on mouse chromosome 11.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Article
- HumanJournal of neurophysiology · 2022Article
- Genetic Landscape ofMolecular syndromology · 2022Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
Dominant loss-of-function mutations in voltage-gated sodium channel NaV1.1 cause Dravet Syndrome, an intractable childhood-onset epilepsy. NaV1.1(+/-) Dravet Syndrome mice in C57BL/6 genetic background exhibit severe seizures, cognitive and social impairments, and premature death. Here we show that Dravet Syndrome mice in pure 129/SvJ genetic background have many fewer seizures and much less premature death than in pure C57BL/6 background. These mice also have a higher threshold for thermally induced seizures, fewer myoclonic seizures, and no cognitive impairment, similar to patients with Genetic Epilepsy with Febrile Seizures Plus. Consistent with this mild phenotype, mutation of NaV1.1 channels has much less physiological effect on neuronal excitability in 129/SvJ mice. In hippocampal slices, the excitability of CA1 Stratum Oriens interneurons is selectively impaired, while the excitability of CA1 pyramidal cells is unaffected. NaV1.1 haploinsufficiency results in increased rheobase and threshold for action potential firing and impaired ability to sustain high-frequency firing. Moreover, deletion of NaV1.1 markedly reduces the amplification and integration of synaptic events, further contributing to reduced excitability of interneurons. Excitability is less impaired in inhibitory neurons of Dravet Syndrome mice in 129/SvJ genetic background. Because specific deletion of NaV1.1 in forebrain GABAergic interneuons is sufficient to cause the symptoms of Dravet Syndrome in mice, our results support the conclusion that the milder phenotype in 129/SvJ mice is caused by lesser impairment of sodium channel function and electrical excitability in their forebrain interneurons. This mild impairment of excitability of interneurons leads to a milder disease phenotype in 129/SvJ mice, similar to Genetic Epilepsy with Febrile Seizures Plus in humans.
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