Molecular bases and dynamisms of learning and memory.

2012 Fiscal Year Final Research Report

• Project Area: Systems molecular ethology to understand the operating principle of the nervous system
• Project/Area Number: 20115006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo 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, 運動・感覚システム研究分野, 参事研究員 (50261839)
• Co-Investigator(Kenkyū-buntansha): MIYASHITA Tomoyuki 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 主任研究員 (70270668)
• Project Period (FY): 2008 – 2012
• Keywords: ショウジョウバエ / 学習記憶 / 遺伝子 / イメージング

Research Abstract

Drosophila is an ideal animal model to investigate molecular and physiological function of memory-related genes. In this study, using Drosophila, we demonstrate following results. 1) Mg2+ block of NMDA receptors is specifically required for long-term memory (LTM) formation through inhibiting expression of suppressor isoform of CREB. 2) increase in cell adhesion molecule, Klingon (Klg) after induction of LTM is an essential for LTM formation and is dependent on Notch. 3) PKA has an inhibitory function in memory consolidation. 4) mild starvation enhance LTM formation via activating CRTC/CREB transcriptional pathway. Regarding memory disorders we show following results. 5) acute inhibition of PKA can ameliorate memory impairment in aged flies. 6) age-related memory impairment (AMI) is not caused by age-related increase in oxidative stress in Drosophila. 7) insulin signaling-dependent developmental defects causes mental retardation. 8) long-term enhancement (LTE) formed in the mushroom bodies of cultured isolated brain is a cellular model of olfactory associative memory.

Research Products

• [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
• [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., and Saitoe M.
  • Journal Title: Science Volume: 339 Pages: 443-446
  • 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., and Saitoe M.
  • Journal Title: J. Physiol. Volume: 591 Pages: 287-302
  • Peer Reviewed
• [Journal Article] Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction. (2013)
  • Author(s): Kamimura K, Ueno K, Nakagawa J, Hamada R, Saitoe M, Maeda N
  • Journal Title: J Cell Biol. Volume: 200 Pages: 219-233
  • Peer Reviewed
• [Journal Article] Mg^<2+> block of Drosophila NMDA receptors is required for long-term memory formation and CREB-dependent gene expression. (2012)
  • Author(s): Miyashita, T., Oda, Y., Horiuchi, J., Yin, J.C., Morimoto, T., and Saitoe M.
  • Journal Title: Neuron Volume: 74 Pages: 887-898
  • Peer Reviewed
• [Journal Article] Mutations in the Drosophila insulin receptor substrate, CHICO, impair olfactory associative learning. (2012)
  • Author(s): Naganos, S., Horiuchi, J., and Saitoe, M.
  • Journal Title: Neurosci. Res. Volume: 73 Pages: 49-55
  • Peer Reviewed
• [Journal Article] Reactive oxygen species are not involved in the onset of age-related memory impairment in Drosophila. (2012)
  • Author(s): Hirano, Y., Kuriyama, Y., Miyashita, T., Horiuchi, J., and Saitoe, M.
  • Journal Title: Genes, Brain and Behavior Volume: 11 Pages: 79-86
  • Peer Reviewed
• [Journal Article] 脳の老化:加齢性記憶障害とその分子機構 (2010)
  • Author(s): 平野恭敬、齊藤 実
  • Journal Title: メディカルバイオ Volume: 7 Pages: 24-29
• [Journal Article] 学習・記憶と分子マーカー (2010)
  • Author(s): 松野元美、齊藤 実
  • Journal Title: 月刊臨床医学 Volume: 12 Pages: 1375-1379
• [Journal Article] 記憶学習の精緻な理解に向けてのモデル動物:ハエ (2010)
  • Author(s): 上野耕平、齊藤 実
  • Journal Title: 生体の科学 Volume: 61 Pages: 17-23
• [Journal Article] Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning. (2010)
  • Author(s): Tamura T, Horiuchi D, Chen, Y.C, Sone M, Miyashita T, Saitoe M, Yoshimura N, Chiang A.S, Okazawa H.
  • Journal Title: J Neurosci. Volume: 30 Pages: 14091-14101
  • Peer Reviewed
• [Journal Article] Acute inhibition of PKA activity at old ages ameliorates age-related memory impairment in Drosophila. (2010)
  • Author(s): Yamazaki, D., Horiuchi, J., Miyashita, T., and Saitoe, M.
  • Journal Title: J. Neurosci. Volume: 30 Pages: 15573-15577
  • Peer Reviewed
• [Journal Article] Genetic dissection of age-related memory impairment in Drosophila. (2010)
  • Author(s): Yamazaki, D., Horiuchi, J., and Saitoe, M.
  • Journal Title: Hirosaki Med. J. Volume: 61 Pages: S26-S33
  • Peer Reviewed
• [Journal Article] The Drosophila CAM Klingon is required for long-term memory formation and is regulated by Notch. (2009)
  • Author(s): Matsuno, M., Horiuchi, J., Tully, T., and Saitoe, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 106 Pages: 310-315
  • Peer Reviewed
• [Journal Article] PKA inhibits a consolidated form of memory in Drosophila. (2008)
  • Author(s): Horiuchi, J., Yamazaki, D., Naganos, S., Aigaki, T., and Saitoe, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 105 Pages: 20976-20981
  • Peer Reviewed
• [Presentation] The rest interval dependent MAPK activation forms and sustains c-fos and CREB transcriptional cycling required for long-term memory. (2012)
  • Author(s): 宮下知之、齊藤 実
  • Organizer: 第35回日本分子生物学会年会ワークショップ「遺伝子発現とタンパク質分解によって産み出される記憶制御のダイナミクス」
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-11
• [Presentation] Long-term enhancement in the mushroom body in cultured Drosophila brain: Cellular substrate for olfactory learning. (2012)
  • Author(s): Ueno K, Saitoe M.
  • Organizer: International symposium on organization and function of the nervous system
  • Place of Presentation: 東京
  • Year and Date: 2012-11-27
• [Presentation] 長期記憶形成に必要な神経-グリア相互作用 (2012)
  • Author(s): 松野元美、齊藤 実
  • Organizer: 日本神経科学大会シンポジウム「個々の神経細胞の働きを俯瞰して見る脳機能」
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-19
• [Presentation] Food deprivation facilitates long-term memory formation through activation of the CREB co-activator, CRTC in Drosophila. (2012)
  • Author(s): Hirano Y, Naganos S, Matsuno M, Ueno K, Miyashita T, Horiuchi J, Saitoe M
  • Organizer: in Neurofly
  • Place of Presentation: Padua, Italy
  • Year and Date: 2012-09-05
• [Presentation] in vivo imaging analysis of neural plasticity in mushroom body neurons. 「Visualization and optic control of neural circuit underlying behavior」 (2011)
  • Author(s): 上野耕平、齊藤 実
  • Organizer: 第34回日本分子生物学会年会ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] Regulation of Drosophila age-related memory impairment by glial cells. (2011)
  • Author(s): Saitoe M
  • Organizer: in Learning and Memory: A Synthesis of Flies and Honeybees Janelia Farm HHMI Conference
  • Place of Presentation: Janelia Farm Research Campus, VA, USA
  • Year and Date: 2011-05-16
• [Presentation] 遺伝子と行動を繋ぐ脳機能の蛍光イメージング解析。「行動は遺伝子でどこまで規定されるか」 (2010)
  • Author(s): 上野耕平、齊藤 実
  • Organizer: 第33回日本分子生物学会年会ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Associative neural plasticity in the mushroom body of Drosophila. (2010)
  • Author(s): Ueno K, Naganos S, Saitoe M
  • Organizer: in System molecular ethology and beyond
  • Place of Presentation: 東京
  • Year and Date: 2010-11-10
• [Presentation] 加齢に伴う記憶力低下の分子機序 (2010)
  • Author(s): 齊藤 実
  • Organizer: 年齢軸生体恒常性研究会シンポジウム 年齢・健康・疾患-生命の統合的理解にむけて
  • Place of Presentation: つくば
  • Year and Date: 2010-03-05
• [Presentation] The Drosophila CAM Klingon is required for memory consolidation via neuron-glia interaction. (2009)
  • Author(s): Matsuno M, Horiuchi J, Tully T, Saitoe M
  • Organizer: 第32回日本分子生物学会年会シンポジウム「神経回路を基盤とするシステム分子行動学」
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] cAMP/PKAシグナリングによる脳の老化機構 (2009)
  • Author(s): 齊藤 実
  • Organizer: 第31回日本基礎老化学会シンポジウム「老化に伴う生体ネットワーク変化の解明に向けた新たなトレンド」
  • Place of Presentation: 東京
  • Year and Date: 2009-10-31
• [Presentation] chico, a Drosophila insulin receptor substrate homolog is required for olfactory learning. (2009)
  • Author(s): Nagano S, Saitoe M
  • Organizer: in Neurobiology of Drosophila.
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
  • Year and Date: 2009-10-01
• [Presentation] Pyruvate Carboxylase, a downstream candidate for cAMP/PKA signaling pathway that regulates age-related memory impairment in Drosophila. (2009)
  • Author(s): Yamazaki D, Saitoe M
  • Organizer: 11th Meeting of Hirosaki International Forum of Medical Science
  • Place of Presentation: 弘前
  • Year and Date: 2009-03-27
• [Presentation] cAMP/PKA signaling pathway that regulates age-related memory impairment in Drosophila. (2008)
  • Author(s): 齊藤 実
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会 シンポジウム「老化と代謝」
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Functional significance of Mg^<2+> block in associative learning and memory. (2008)
  • Author(s): Miyashita T, Horiuchi J, Saitoe M
  • Organizer: in Learning and Memory: A Synthesis of Flies and Honeybees Janelia Farm HHMI Conference
  • Place of Presentation: Janelia Farm Research Campus, VA, USA
  • Year and Date: 2008-11-12
• [Remarks]
  • URL: http://www.igakuken.or.jp/memory/
• [Remarks] マスコミ報道その他 1. Learning and memory: Austerity measures for memory: Research Highlight in Nature Rev Neurosci 14, 159(2013).
• [Remarks] 2.「空腹時記憶向上」科学新聞(2013. 2. 8)
• [Remarks] 3.「記憶力は"空腹状態で向上"」NHK おはよう日本(2013. 2.1)
• [Remarks] 4.「おなかが空くと記憶力アップ 都医学総研、ハエで確認」他。日本経済新聞、時事通信、読売新聞(夕刊)、毎日新聞(2013.1.25)
• [Remarks] 5. Tabone CJ, Ramaswami M. Neuron 74, 767-769(2012)にて同号に発表した論文の特集を組まれる Is NMDA Receptor-Coincidence Detection Required for Learning and Memory?
• [Remarks] 6.「マグネシウムにより記憶を調節」東京新聞(2012.6.7)
• [Remarks] 7.「マグネシウムブロックによる記憶調節」NHKおはよう日本他 研究紹介(2012. 6. 7)
• [Remarks] 8. 物忘れ仕組み解明期待 読売新聞(多摩版) 2009.2.18