RT Journal Article
SR Electronic
T1 Na<sub>v</sub>1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying an <em>Scn1a</em> Gene Mutation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5903
OP 5914
DO 10.1523/JNEUROSCI.5270-06.2007
VO 27
IS 22
A1 Ogiwara, Ikuo
A1 Miyamoto, Hiroyuki
A1 Morita, Noriyuki
A1 Atapour, Nafiseh
A1 Mazaki, Emi
A1 Inoue, Ikuyo
A1 Takeuchi, Tamaki
A1 Itohara, Shigeyoshi
A1 Yanagawa, Yuchio
A1 Obata, Kunihiko
A1 Furuichi, Teiichi
A1 Hensch, Takao K.
A1 Yamakawa, Kazuhiro
YR 2007
UL http://www.jneurosci.org/content/27/22/5903.abstract
AB 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.