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Molecular and neural bases of memory dynamism in Drosophila

Planned Research

Project AreaPrinciples of memory dynamism elucidated from a diversity of learning systems
Project/Area Number 25115006
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

SAITOE Minoru  公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 基盤技術研究センター長 (50261839)

Co-Investigator(Kenkyū-buntansha) 粂 和彦  名古屋市立大学, 大学院薬学研究科, 教授 (30251218)
上野 太郎  東邦大学, 理学部, 講師 (30648267)
坂井 貴臣  首都大学東京, 理工学研究科, 准教授 (50322730)
佐藤 守俊  東京大学, 大学院総合文化研究科, 准教授 (00323501)
Project Period (FY) 2013-06-28 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥147,160,000 (Direct Cost: ¥113,200,000、Indirect Cost: ¥33,960,000)
Fiscal Year 2017: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
Fiscal Year 2016: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
Fiscal Year 2015: ¥32,890,000 (Direct Cost: ¥25,300,000、Indirect Cost: ¥7,590,000)
Fiscal Year 2014: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000)
Fiscal Year 2013: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000)
Keywords記憶 / ショウジョウバエ / ドーパミン / 老化 / グリア / 連合学習 / 強化シグナル / 逆行性シグナル / 一酸化炭素 / 神経科学 / シグナル伝達 / 行動学 / 昆虫 / 学習記憶 / 脳・神経 / 生理学 / シナプス可塑性 / 単離培養脳
Outline of Final Research Achievements

Taking advantages of Drosophila, we discovered how dopaminergic neurons reinforce association of sensory information to produce associative memory and identified novel mode of dopamine release induced by activity of postsynaptic neurons. Regarding consolidation of labile short-term memory to stable long-term memory, we found that c-fos/CREB transcriptional cycling formed by MAPK, which is activated during resting intervals of spaced training, encodes long-term memory in memory engram neurons, and identified a novel neuron-glia interaction by which glial cells express genes required for long-term memory formation. We also identified novel transcriptional machineries required for maintenance of long-term memory. Regarding alternation of memory mechanism upon aging, we found that age-related increase in activity of pyruvate carboxylase attenuates production D-serine in glial cells thereby impairs middle-term memory in aged flies.

Report

(6 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (52 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (27 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Book (1 results) Remarks (5 results) Funded Workshop (1 results)

  • [Int'l Joint Research] University of California, Barkeley(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Korea University(韓国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] A Drosophila ex vivo model of olfactory appetitive learning2017

    • Author(s)
      Suzuki-Sawano Ema、Ueno Kohei、Naganos Shintaro、Sawano Yoshihiro、Horiuchi Junjiro、Saitoe Minoru
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-17955-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coincident postsynaptic activity gates presynaptic dopamine release to induce plasticity in Drosophila mushroom bodies.2017

    • Author(s)
      Ueno K, Suzuki E, Naganos S, Ofusa K, Horiuchi J, Saitoe M.
    • Journal Title

      eLife

      Volume: 6 Pages: 1-18

    • DOI

      10.7554/elife.21076

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Shifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies.2016

    • Author(s)
      Hirano Y, Ihara K, Masuda T, Yamamoto T, Iwata I, Takahashi A, Awata H, Nakamura N, Takakura M, Suzuki Y, Horiuchi J, Okuno H, Saitoe M.
    • Journal Title

      Nat Commun.

      Volume: 7 Issue: 1 Pages: 13471-13471

    • DOI

      10.1038/ncomms13471

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity2016

    • Author(s)
      Naganos S, Ueno K, Horiuchi J, Saitoe M
    • Journal Title

      Molecular Brain

      Volume: Apr 6;9:37 Issue: 1 Pages: 1-10

    • DOI

      10.1186/s13041-016-0217-3

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Phosphorylation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Truncated Casein Kinase 1δ Triggers Mislocalization and Accumulation of TDP-43.2016

    • Author(s)
      Nonaka T, Suzuki G, Tanaka Y, Kametani F, Hirai S, Okado H, Miyashita T, Saitoe M, Akiyama H, Masai H, Hasegawa M.
    • Journal Title

      The journal of Biological Chemistry

      Volume: 291 Issue: 11 Pages: 5473-83

    • DOI

      10.1074/jbc.m115.695379

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ショウジョウバエだから分かる学習記憶のメカニズム2016

    • Author(s)
      長野慎太郎、齊藤 実
    • Journal Title

      生体の科学

      Volume: 61 Pages: 13-16

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Long-Term Memory Formation in Drosophila Requires Training-Dependent Glial Transcription2015

    • Author(s)
      Matsuno M, Horiuchi J, Yuasa Y, Ofusa K, Miyashita T, Masuda T, and Saitoe M
    • Journal Title

      The Journal of Neuroscience

      Volume: 35 Issue: 14 Pages: 5557-5565

    • DOI

      10.1523/jneurosci.3865-14.2015

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 加齢による記憶力の低下とグリア細胞2015

    • Author(s)
      齊藤 実・堀内純二郎・山崎大介
    • Journal Title

      Clinical Neuroscience 月刊臨床神経科学

      Volume: 33 Pages: 1084-1085

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Glial dysfunction causes age-related memory impairment in Drosophila.2014

    • Author(s)
      Yamazaki D, Horiuchi J, Ueno K, Ueno T, Saeki S, Matsuno M, Naganos S, Miyashita T, Hirano Y, Nishikawa H, Taoka M, Yamauchi Y, Isobe T, Honda Y, Kodama T, Masuda T, Saitoe M
    • Journal Title

      Neuron

      Volume: 84 Issue: 4 Pages: 753-763

    • DOI

      10.1016/j.neuron.2014.09.039

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hunger-driven modulation in brain functions2014

    • Author(s)
      Hirano Y, Saitoe M.
    • Journal Title

      Brain Nerve

      Volume: 66 Pages: 41-8

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Hunger-driven modulation in brain functions.2014

    • Author(s)
      Hirano Y, Saitoe M
    • Journal Title

      Brain Nerve

      Volume: 66 Pages: 41-48

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Hunger and memory; CRTC coordinates long-term memory with the physiological state, hunger.2013

    • Author(s)
      Hirano Y, Saitoe M.
    • Journal Title

      Commun Integr Biol.

      Volume: 6 Issue: 5 Pages: e25152-e25152

    • DOI

      10.4161/cib.25152

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fasting launches CRTC to facilitate long-term memory formation in Drosophila.2013

    • Author(s)
      Hirano, Y., Masuda, T., Naganos, S., Matsuno, M., Ueno, K., Miyashita, T., Horiuchi, J., Saitoe, M.
    • Journal Title

      Science

      Volume: 339 Issue: 6118 Pages: 443-446

    • DOI

      10.1126/science.1227170

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction2013

    • Author(s)
      Kamimura K., Ueno K., Nakagawa J., Hamada R., Saitoe M., and Maeda N
    • Journal Title

      J. Cell Biol

      Volume: 200 Issue: 2 Pages: 219-233

    • DOI

      10.1083/jcb.201207036

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain.2013

    • Author(s)
      Ueno, K., Naganos, S., Hirano, Y., Horiuchi, J., Saitoe, M.
    • Journal Title

      J Physiol.

      Volume: 591 Issue: 1 Pages: 287-302

    • DOI

      10.1113/jphysiol.2012.242909

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 記憶改善に向けた新たな進展:軽度の空腹状態は長期記憶形成を促進する2013

    • Author(s)
      平野恭敬、齊藤 実
    • Journal Title

      細胞工学

      Volume: 32 Pages: 452-453

    • Related Report
      2013 Annual Research Report
  • [Presentation] 電気化学的手法を用いた匂い連合学習を担う単一ドパミン神経機能の解明2017

    • Author(s)
      長野慎太郎、齊藤 実
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ショウジョウバエ微小脳による記憶回路動作機構の分子生理学的解析2017

    • Author(s)
      齊藤 実
    • Organizer
      第40回日本神経科学学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 共役入力を受けた後シナプス神経細胞はシナプス前終末cGMP/リアノジン受容体シグナルを活性化しドーパミンを放出する2017

    • Author(s)
      上野耕平、齊藤 実
    • Organizer
      第40回日本神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 電気化学的手法を用いたショウジョウバエの脳内モノアミン放出のリアルタイム定量解析2017

    • Author(s)
      長野慎太郎、齊藤 実
    • Organizer
      第40回日本神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 加齢性長期記憶障害は記憶固定時のドーパミン神経の過剰活性化による2017

    • Author(s)
      松野元美、堀内純二郎、増田朋子、大房京子、齊藤 実
    • Organizer
      第40回日本神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] グリアのグルタミン酸小胞放出はショウジョウバエの連合学習に必要な嫌悪情報を伝達する2017

    • Author(s)
      宮下知之、村上佳奈子、齊藤 実
    • Organizer
      第40回日本神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 加齢体では繰り返し学習後の神経細胞過興奮により長期記憶が障害される2016

    • Author(s)
      松野元美、堀内純二郎、大房京子、増田朋子、齊藤 実
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] グリア細胞からの小胞性グルタミン酸放出は連合学習に必要である2016

    • Author(s)
      村上佳奈子、宮下知之、菊池絵美、宮地孝明、森山芳則、齊藤 実
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ドーパミン放出の標的細胞による新たなゲーティング機構2016

    • Author(s)
      齊藤 実
    • Organizer
      第46回日本神経精神薬理学会シンポジウム
    • Place of Presentation
      ソウルCOEX(韓国)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 繰り返し学習の休息は長期記憶符号化神経細胞においてc-fos/creb転写サイクル生成のために必要である2015

    • Author(s)
      宮下知之、齊藤 実
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Dopamine release is gated by coincidentally stimulated postsynaptic neurons to reinforce plasticity2015

    • Author(s)
      Ueno K, Saitoe M
    • Organizer
      Neuroscience 2015
    • Place of Presentation
      米国シカゴ
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dopamine receptor activities regulate learning-dependent odor preference changes in Drosophila.2015

    • Author(s)
      Naganos S, Saitoe M
    • Organizer
      Neuroscience 2015
    • Place of Presentation
      米国シカゴ
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規On-demand型ドーパミン放出機構について2015

    • Author(s)
      齊藤 実
    • Organizer
      新学術領域「記憶ダイナミズム」数理シンポジウム
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Presynaptic dopamine release is gated by postsynaptic activity in Drosophila brain2015

    • Author(s)
      上野耕平、齊藤 実
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Neuron-glia interactions involved in memory formation and age-related memory impairment in Drosophila2015

    • Author(s)
      齊藤 実
    • Organizer
      新学術領域「グリアアセンブリ」夏の国際ワークショップ
    • Place of Presentation
      岡崎コンファレンスセンター(愛知県岡崎市)
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 単離脳解析から見出されたドパミン放出の新機構2014

    • Author(s)
      上野耕平、齊藤 実
    • Organizer
      平成26年度包括脳ネットワーク冬のシンポジウム
    • Place of Presentation
      ホテル東京ガーデンパレス(東京都文京区)
    • Year and Date
      2014-12-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Dopamine release is gated by coincident stimulation of mushroom body neurons to establish plasticity2014

    • Author(s)
      上野耕平、齊藤 実
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Aging reduces glial protection from memory-induced cell death2014

    • Author(s)
      松野元美、堀内純二郎、齊藤 実
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Coincident stimulation induces dopamine release required for long-term enhancement of Ca2+ influx in mushroom body neurons.2014

    • Author(s)
      Saitoe M, Ueno K.
    • Organizer
      Learning and Memory: A Synthesis of Flies and Honeybees
    • Place of Presentation
      Janelia Farm Research Campus(USA)
    • Year and Date
      2014-09-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Glial regulation of age-related memory impairment in Drosophila2014

    • Author(s)
      Horiuchi J, Matsuno M, Masuda T, Saitoe M.
    • Organizer
      Learning and Memory: A Synthesis of Flies and Honeybees
    • Place of Presentation
      Janelia Farm Research Campus(USA)
    • Year and Date
      2014-09-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] The mechanisms of learning dependent odor preference changes following olfactory conditioning2014

    • Author(s)
      長野慎太郎、上野耕平、川端有紀、齊藤 実
    • Organizer
      日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 長期記憶形成に必要なグリア転写因子Repoによる遺伝子発現2013

    • Author(s)
      松野元美、齊藤 実
    • Organizer
      記憶回路研究会
    • Place of Presentation
      岡崎生理学研究所
    • Related Report
      2013 Annual Research Report
  • [Presentation] On-demand dopamine release, triggered by coincident stimuli, determines Drosophila mushroom body plasticity2013

    • Author(s)
      Ueno K, Horiuchi J, Saitoe M.
    • Organizer
      Cell Symposia: Networked Brain
    • Place of Presentation
      Sheraton San Diego Hotel and Marina, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Long-term memory formation requires neuron-glial signaling to induce glial protein synthesis.2013

    • Author(s)
      Matsuno M, Horiuchi J, Saitoe M.
    • Organizer
      Cell Symposia: Networked Brain
    • Place of Presentation
      Sheraton San Diego Hotel and Marina, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Age-related memory impairment in Drosophila is caused by an oxidative stress-independent impairment of glial neuromodulator release.2013

    • Author(s)
      Horiuchi J, Yamazaki D, Saitoe M.
    • Organizer
      Neurobiology of Drosophila
    • Place of Presentation
      Cold Spring Harbor Laboratory
    • Related Report
      2013 Annual Research Report
  • [Presentation] Coincident stimulation induces dopamine release required for long-term enhancement of Ca2+ influx in mushroom body neurons.2013

    • Author(s)
      Ueno K, Saitoe M.
    • Organizer
      Neurobiology of Drosophila
    • Place of Presentation
      Cold Spring Harbor Laboratory, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Olfactory aversive conditioning forms two distinct memory components in Drosophila.2013

    • Author(s)
      Naganos S, Ueno K, Horiuchi J, Saitoe M.
    • Organizer
      Neurobiology of Drosophila
    • Place of Presentation
      Cold Spring Harbor Laboratory, USA
    • Related Report
      2013 Annual Research Report
  • [Book] 基礎分子生物学Ⅱ:遺伝子発現制御機構―クロマチン,転写制御,エピジェネティクス2016

    • Author(s)
      平野恭敬、齊藤 実
    • Total Pages
      250
    • Publisher
      東京化学同人
    • Related Report
      2016 Annual Research Report
  • [Remarks] 学習記憶プロジェクト

    • URL

      http://www.igakuken.or.jp/memory/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京都医学総合研究所学習記憶プロジェクト

    • URL

      http://www.igakuken.or.jp/memory/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 学習記憶とその障害の分子機構の解明プロジェクトHP

    • URL

      http://www.igakuken.or.jp/memory/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 学習記憶プロジェクトHP

    • URL

      http://www.igakuken.or.jp/memory/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京都医学総合研究所学習記憶プロジェクト

    • URL

      http://www.igakuken.or.jp/memory/

    • Related Report
      2013 Annual Research Report
  • [Funded Workshop] Memory Dynamism2015

    • Place of Presentation
      京都大学稲森ホール(京都府京都市)
    • Year and Date
      2015-11-06
    • Related Report
      2015 Annual Research Report

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Published: 2013-07-10   Modified: 2022-02-07  

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