ArticleNeurobiology of disease2013
Preferential inactivation of Scn1a in parvalbumin interneurons increases seizure susceptibility.
Article in Neurobiology of disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 130 citations in OpenAlex.
- Developmental dysregulation of chandelier cell excitability in a mouse model of Dravet Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Developmental progression of respiratory dysfunction in a mouse model of Dravet syndrome.JCI insight · 2025Article
- Transgenic mouse models of sodium and potassium channelopathies in epilepsy: insights into disease mechanisms and therapeutics.Bioscience reports · 2025Review
- Depolarization block induction via slow NaScientific reports · 2025Article
- 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
- Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction.Biochemical Society transactions · 2024Review
- Brain expression profiles of twoTranslational neuroscience · 2024Article
- Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair.Communications biology · 2023Review
- Retinal Tissue Shows Glial Changes in a Dravet Syndrome Knock-in Mouse Model.International journal of molecular sciences · 2023Article
- Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome.Brain communications · 2023Article
- Developmental changes in brain activity of heterozygousFrontiers in neurology · 2023Article
- Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models ofeLife · 2022Article
- Article
- 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
- Pharmacological determination of the fractional block of Nav channels required to impair neuronal excitability andFrontiers in cellular neuroscience · 2022Article
- Reversing frontal disinhibition rescues behavioural deficits in models of CACNA1A-associated neurodevelopment disorders.Molecular psychiatry · 2021Article
- Generation and Characterization of theLife (Basel, Switzerland) · 2021Article
- Application of single cell genomics to focal epilepsies: A call to action.Brain pathology (Zurich, Switzerland) · 2021Review
- Deletion of a non-canonical regulatory sequence causes loss of Scn1a expression and epileptic phenotypes in mice.Genome medicine · 2021Article
- GABAergic Gene Regulatory Elements Used in Adeno-Associated Viral Vectors.Frontiers in neurology · 2021Review
16 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials in electrically excitable cells. Dominant mutations in SCN1A, which encodes the Nav1.1 VGSC α-subunit, underlie several forms of epilepsy, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+). Electrophysiological analyses of DS and GEFS+ mouse models have led to the hypothesis that SCN1A mutations reduce the excitability of inhibitory cortical and hippocampal interneurons. To more directly examine the relative contribution of inhibitory interneurons and excitatory pyramidal cells to SCN1A-derived epilepsy, we first compared the expression of Nav1.1 in inhibitory parvalbumin (PV) interneurons and excitatory neurons from P22 mice using fluorescent immunohistochemistry. In the hippocampus and neocortex, 69% of Nav1.1 immunoreactive neurons were also positive for PV. In contrast, 13% and 5% of Nav1.1 positive cells in the hippocampus and neocortex, respectively, were found to co-localize with excitatory cells identified by CaMK2α immunoreactivity. Next, we reduced the expression of Scn1a in either a subset of interneurons (mainly PV interneurons) or excitatory cells by crossing mice heterozygous for a floxed Scn1a allele to either the Ppp1r2-Cre or EMX1-Cre transgenic lines, respectively. The inactivation of one Scn1a allele in interneurons of the neocortex and hippocampus was sufficient to reduce thresholds to flurothyl- and hyperthermia-induced seizures, whereas thresholds were unaltered following inactivation in excitatory cells. Reduced interneuron Scn1a expression also resulted in the generation of spontaneous seizures. These findings provide direct evidence for an important role of PV interneurons in the pathogenesis of Scn1a-derived epilepsies.
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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.