ArticleAnnals of neurology2013
CaV 2.1 ablation in cortical interneurons selectively impairs fast-spiking basket cells and causes generalized seizures.
Article in Annals of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 112 citations in OpenAlex.
- Reduced inhibition of hippocampal adult-born granule cells by parvalbumin interneurons after TBI.bioRxiv : the preprint server for biology · 2026Article
- Neurodevelopmental Alterations in Inhibitory Interneurons of Cortex, Hippocampus, and Striatum of Genetic Absence Epilepsy Rats.CNS neuroscience & therapeutics · 2026Article
- Parvalbumin interneuron activation rescues both seizures and impaired social novelty in digenic absence epilepsy mice.Science advances · 2026Article
- Human neuronal networks on micro-electrode arrays as a tool to assess genotype-phenotype correlation in CACNA1A-related disorders.Stem cell reports · 2026Article
- Spatial genomics of AAV vectors reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo.Nature biotechnology · 2026Article
- CACNA1A loss-of-function affects neurogenesis in human iPSC-derived neural models.Cellular and molecular life sciences : CMLS · 2025Article
- CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability.Brain : a journal of neurology · 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
- In vitro human ion channel assays predictive of drug-induced seizure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Parvalbumin interneurons: the dark and bright sides of a key playmaker of neural circuits and behavior.Frontiers in cellular neuroscience · 2025Review
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.Cells · 2024Review
- Parvalbumin interneuron impairment causes synaptic transmission deficits and seizures in SCN8A developmental and epileptic encephalopathy.JCI insight · 2024Article
- Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy.Neural regeneration research · 2024Article
- A neurodevelopmental disorder caused by a dysfunctionaleNeurologicalSci · 2023Article
- Differential cortical activation patterns: pioneering sub-classification of tinnitus with and without hyperacusis by combining audiometry, gamma oscillations, and hemodynamics.Frontiers in neuroscience · 2023Article
- Interneuron odyssey: molecular mechanisms of tangential migration.Frontiers in neural circuits · 2023Review
- An efficient rAAV vector for protein expression in cortical parvalbumin expressing interneurons.Scientific reports · 2022Article
- Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition.eLife · 2022Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveBoth the neuronal populations and mechanisms responsible for generalized spike-wave absence seizures are poorly understood. In mutant mice carrying loss-of-function (LOF) mutations in Cacna1a, which encodes the α1 pore-forming subunit of CaV 2.1 (P/Q-type) voltage-gated Ca(2+) channels, generalized spike-wave seizures have been suggested to result from excessive bursting of thalamocortical cells. However, other cellular populations including cortical inhibitory interneurons may contribute to this phenotype. We investigated how different cortical interneuron subtypes are affected by the loss of CaV 2.1 channel function and how this contributes to the onset of generalized epilepsy.
methodsWe designed genetic strategies to induce a selective Cacna1a LOF mutation in different cortical γ-aminobutyric acidergic (GABAergic) and/or glutamatergic neuronal populations in mice. We assessed the cellular and network consequences of these mutations by combining immunohistochemical assays, in vitro physiology, optogenetics, and in vivo video electroencephalographic recordings.
resultsWe demonstrate that selective Cacna1a LOF from a subset of cortical interneurons, including parvalbumin (PV)(+) and somatostatin (SST)(+) interneurons, results in severe generalized epilepsy. Loss of CaV 2.1 channel function compromises GABA release from PV(+) but not SST(+) interneurons. Moreover, thalamocortical projection neurons do not show enhanced bursting in these mutants, suggesting that this feature is not essential for the development of generalized spike-wave seizures. Notably, the concurrent removal of CaV 2.1 channels in cortical pyramidal cells and interneurons considerably lessens seizure severity by decreasing cortical excitability.
interpretationOur findings demonstrate that conditional ablation of CaV 2.1 channel function from cortical PV(+) interneurons alters GABA release from these cells, impairs their ability to constrain cortical pyramidal cell excitability, and is sufficient to cause generalized seizures.
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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.