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演題詳細

Poster

シナプス
Synapse

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

成熟小脳において1型IP3受容体はプルキンエ細胞の樹状突起スパインの形態制御に関わる
IP3R1 regulates cerebellar circuits by maintaining the spine morphology of Purkinje cells in adult mice

  • P2-029
  • 菅原 健之 / Takeyuki Sugawara:1 久恒 智博 / Chihiro Hisatsune:1 Le Tung Dinh / Tung Dinh Le:2 端川 勉 / Tsutomu Hashikawa:3 廣野 守俊 / Moritoshi Hirono:2 服部 光治 / Mitsuharu Hattori:4 永雄 総一 / Soichi Nagao:2 御子柴 克彦 / Katsuhiko Mikoshiba:1,5 
  • 1:理研BSI発生神経生物 / Lab. for Developmental Neurobiology, RIKEN Brain Science Institute 2:理研BSI運動学習制御 / Lab. for Motor Learning Control, RIKEN Brain Science Institute 3:理研BSI神経構築技術開発チーム / Lab. for Neural Architecture, RIKEN Brain Science Institute 4:名古屋市大薬病態生化学 / Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University 5:科学技術振興機構 カルシウム振動プロジェクト / Calcium Oscillation Project, ICORP-SORST 

Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ channel, and the type 1 IP3R (IP3R1) is predominantly expressed in the central nervous system, especially cerebellar Purkinje cells (PC). Previously, we demonstrated that IP3R1-null mice display severe dystonic movements and ataxia, and die within postnatal third weeks. However, the specific contribution of PC IP3R1 in the adult mouse brain function is still unknown. Here we show that IP3R1 in PCs plays a crucial role in the maintenance of parallel fiber (PF)-PC synaptic circuits in the mature cerebellum. Strikingly, adult mice lacking IP3R1 specifically in PCs (L7-Cre;Itpr1flox/flox) showed dramatic increase in spine density and spine length of PCs, despite having normal spines during development. In addition, the abnormally rearranged PF-PC synaptic circuits in mature cerebellum caused unexpectedly severe ataxia in the adult mice. Furthermore, L7-Cre;Itpr1flox/flox mice impaired long-term depression at PF-PC synapses and adaptation of optokinetic response, a simple form of motor learning. Our findings reveal a specific role for IP3R1 in PCs not only as an intracellular mediator of cerebellar synaptic plasticity induction, but also as a critical regulator of PF-PC synaptic circuit maintenance in the mature cerebellum in vivo; this mechanism may underlie motor coordination and learning in adults.

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