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Memory traces and tags in the brain

開催日 2014/9/11
時間 9:00 - 11:00
会場 Room B(501)
Chairperson(s) 奥野 浩行 / Hiroyuki Okuno (京都大学大学院 医学研究科 メディカルイノベーションセンター / Medical Innovation Center, Kyoto University Graduate School of Medicine, Japan)
尾藤 晴彦 / Haruhiko Bito (東京大学大学院 医学系研究科 神経生化学分野 / Department of Neurochemistry, The University of Tokyo Graduate School of Medicine, Japan)

Signaling from synapse to the nucleus and imaging of active neuronal ensembles

  • S1-B-1-1
  • 尾藤 晴彦 / Haruhiko Bito:1,2 井上 昌俊 / Masatoshi Inoue:1,2 野中 美応 / Mio Nonaka:1 栁下-姜 楠 / Nan Yagishita-Kyo:1,2 川島 尚之 / Takashi Kawashima:1 鈴木 敢三 / Kanzo Suzuki:1,2 石井 雄一郎 / Yuichiro Ishii:1,2 藤井 哉 / Hajime Fujii:1 遠藤 俊裕 / Toshihiro Endo:1 後藤 愛佳 / Manaka Goto:1 児山 博亮 / Hiroaki Koyama:1 竹本-木村 さやか / Sayaka Takemoto-Kimura:1 金 亮 / Ryang Kim:1,2 
  • 1:東京大院・医・神経生化 / Dept Neurochem, Univ of Tokyo Grad Sch Med, Tokyo, Japan 2:CREST-JST / CREST-JST, Japan 

Over the past years, we have systematically investigated the molecular basis of the signaling from synapses to the nucleus during synaptic plasticity. Initially, an activity-dependent protein kinase cascade CaMKK-CaMKIV critically controls the amplitude and time course of phosphorylation of a nuclear transcription factor CREB downstream of synaptic activity. This event, in turn, activates a plethora of adaptive transcriptional responses within a neuronal circuit. How then can a cell-wide gene induction event influence local onset of plasticity without loss of input specificity? To address this question, we investigated both nuclear and synaptic machineries that governed the induction and the subsequent dendritic delivery of Arc/Arg3.1 protein in activated neurons. We thus identified a potent synaptic activity-responsive element (SARE) in the promoter/enhancer region of Arc gene. Strikingly, this SARE of Arc gene consisted of a unique cluster of binding sites for CREB, MEF2 and SRF/TCF, each of which significantly contributing to converting synaptic responses into a transcriptional one. Recently, we capitalized on our knowledge of the modular structure of SARE to create a synthetic activity-induced promoter E-SARE, which was 30 times more potent than the widely used c-fos promoter. E-SARE-driven viral reporters enabled live mapping and recording from activity-regulated neurons and circuits in various areas of the brain in vivo. Current efforts are being focused to take advantage of our precise understanding of the Arc promoter to image, dissect and manipulate the behavior of specific neuronal circuits in which the signaling from synapses to the nucleus has been enhanced. These experiments will help decipher the intricate and interactive relationship between the information encoded in the genome and the ongoing synaptic activity during long-term memory formation and maintenance in the brain.

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