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Ion Channels and Excitable Membranes

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Neuron-type-specific gene deletion reveals a previously unrecognized Nav1.1 distribution in excitatory neurons

  • P2-002
  • 荻原 郁夫 / Ikuo Ogiwara:1 岩里 琢治 / Takuji Iwasato:2,3,4 山形 哲司 / Tetsushi Yamagata:1 眞崎 恵美 / Emi Mazaki:1 柳川 右千夫 / Yuchio Yanagawa:5,6 玉巻 伸章 / Nobuaki Tamamaki:7 糸原 重美 / Shigeyoshi Itohara:2,8 山川 和弘 / Kazuhiro Yamakawa:1 
  • 1:理研BSI神経遺伝 / Lab Neurogenet, RIKEN BSI, Saitama, Japan 2:理研BSI行動遺伝学 / Lab Behav Genet, RIKEN BSI, Saitama, Japan 3:国立遺伝研個体遺伝形質遺伝 / Div Neurogenet, Natl Inst Genet, Shizuoka, Japan 4:総研大院遺伝学 / Dept Genet, Grad Univ Advanced Studies (SOKENDAI), Shizuoka, Japan 5:群馬大院医遺伝発達行動 / Dept Genet and Behav Neurosci, Gunma Univ Grad Sch Med, Gunma, Japan 6:JST CREST / JST CREST, Tokyo, Japan 7:熊本大院生命科学・医脳回路構造 / Dept Morphol Neural Sci, Grad Sch Med Sciences, Kumamoto Univ, Kumamoto, Japan 8:JST FIRST / FIRST, JST, Tokyo, Japan 

Mutations in SCN1A gene encoding voltage-gated sodium channel Nav1.1 are associated with intractable childhood epilepsy. We recently reported a predominant Nav1.1 localization to the axon initial segments (AISs) of parvalbumin-positive (PV) inhibitory neurons, and epileptic seizures in mice with specific Scn1a gene deletion in PV cells using PV-Cre. We also reported that excitatory neuron-specific gene deletion mediated by Emx1-Cre reduced the risk of sudden death in epilepsy, although Nav1.1 expression in excitatory neurons has not been recognized in our previous study. We here report a previously unrecognized Nav1.1 distribution in excitatory neurons. While PV cell-specific deletion apparently removes Nav1.1 signals in the AISs of PV neurons, Nav1.1 signals still remain in some regions including the axon-like fibers of a subpopulation of neocortical layer V pyramidal cells and the middle one-third of hippocampal dentate gyrus molecular layer where perforant path fibers of medial (rather than lateral) entorhinal cortex excitatory neurons terminate. Emx1-Cre-dependent deletion specifically removes these Nav1.1 signals. Furthermore, Nav1.1 signals in thalamo-cortical excitatory projection neuron axons that arborize in layer IV barrel fields of somatosensory cortex disappear with PV-Cre-dependent elimination but are unaffected by Emx1-Cre dependent elimination. Moreover, no apparent Nav1.1 signals are observed in hippocampal pyramidal somata, where Nav1.1 has been generally thought to be densely localized, even in control mice. Nav1.1 expression in hippocampal pyramidal somata is also negative in the mice expressing GFP under the control of Scn1a promoter. Overall, these results provide solid evidence for Nav1.1 expression in distinct subpopulations of excitatory neurons.

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