Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying an Scn1a Gene Mutation
By I. Ogiwara, H. Miyamoto, N. Morita, N. Atapour, E. Mazaki, I. Inoue, T. Takeuchi, S. Itohara, Y. Yanagawa, K. Obata and 3 more. Journal of Neuroscience, 2007
825 citations recorded by the source corpus.
Loss-of-function mutations in human SCN1A gene encoding Nav1.1 are associated with a severe epileptic disorder known as severe myoclonic epilepsy in infancy. Here, we generated and characterized a knock-in mouse line with a loss-of-function nonsense mutation in the Scn1a gene. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. Immunohistochemical analyses revealed that, in the developing neocortex, Nav1.1 was clustered predominantly at the axon initial segments of parvalbumin-positive (PV) interneurons. In heterozygous knock-in mice, trains of evoked action potentials in these fast-spiking, inhibitory cells exhibited pronounced spike amplitude decrement late in the burst. Our data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and, furthermore, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice.
Subfields: Cellular and Molecular Neuroscience, Genetics, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/ecdb3cd5ad65aafc4a08a9b0056813529892d2d9
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Citations in the corpus
- FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders (2015, positive): “This isoform is preferentially expressed in GABAergic interneurons (Cheah et al., 2012; Han et al., 2012; Ogiwara et al., 2007; Yu et al., 2006) and the increased proportion of cells with this sodium channel phenotype is consistent with a greater proportion of GABAergic neurons in cortical…”
- Signal processing in the axon initial segment. (2012, neutral): “1 subtype is also found in the AIS of GABAergic interneurons, retinal ganglion cells, and spinal cord neurons (Duflocq et al., 2008; Lorincz and Nusser, 2008, 2010; Ogiwara et al., 2007; VanWart et al., 2007).”
- β-Hydroxybutyrate (2017, positive): “The worlds of epilepsy and dementia have been linked through the finding that mouse models of Alzheimer’s disease show neuronal hyperexcitability and epileptiform spikes from dysfunctional inhibitory interneurons (97, 135).”
- Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function (2014, background): “1 immunoreactivity is primarily present in the axons of these cells (49), both fast-spiking action potential phenotype and fast signal propagation in the axon will be affected.”