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Signal Transduction and Modulation

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

mGluR1α-mediated excitation of cerebellar GABAergic interneurons requires both G protein-dependent and Src-ERK1/2-dependent signaling pathways

  • P2-058
  • 久保田 英雄 / Hideo Kubota:1 永雄 総一 / Soichi Nagao:2 小幡 邦彦 / Kunihiko Obata:3 廣野 守俊 / Moritoshi Hirono:2,3,4 
  • 1:東京医歯大・医病・材料部 / Materials Management, Medical Hospital, Tokyo Medical and Dental Univ, Tokyo, Japan 2:理研BSI運動学習制御 / Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Saitama, Japan 3:理研BSI小幡研究ユニット / Obata Research Unit, RIKEN Brain Science Institute, Saitama, Japan 4:同志社大院脳科学研究科チャネル病態生理部門 / Organization for Advanced Research and Education, Doshisha University, Kyoto, Japan 

Stimulation of type I metabotropic glutamate receptors (mGluR1/5) in several neuronal types induces slow excitatory responses through activation of transient receptor potential canonical (TRPC) channels. GABAergic cerebellar molecular layer interneurons (MLIs) modulate firing patterns of Purkinje cells (PCs), which play a key role in cerebellar information processing. MLIs express mGluR1, and activation of mGluR1 induces an inward current, but its precise intracellular signaling pathways are unknown. We found that mGluR1α activation facilitated spontaneous firing of mouse cerebellar MLIs through an inward current mediated by TRPC1 channels. This mGluR1α-mediated inward current depends on both G protein-dependent and -independent pathways. The nonselective protein tyrosine kinase inhibitors genistein and AG490 as well as the selective extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors PD98059 and SL327 suppressed the mGluR1α-current responses. Following G protein blockade, the residual mGluR1α-mediated inward current was significantly reduced by the selective Src kinase inhibitor PP2. In contrast to cerebellar PCs, GABAB receptor activation in MLIs did not alter the mGluR1α-mediated inward current, suggesting that there is no cross-talk between mGluR1α and GABAB receptors in MLIs. Thus, activation of mGluR1α facilitates firing of MLIs through the TRPC1-mediated inward current, which depends on not only G protein-dependent but also Src-ERK1/2-dependent signaling pathways, and consequently depresses the excitability of cerebellar PCs.

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