Elucidation of systems consolidation mechanisms underlying memory trace formation by sensory inputs

• Project/Area Number: 20K15910
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: The University of Tokyo
• Principal Investigator: MINATOHARA KEIICHIRO 東京大学, 大学院医学系研究科(医学部), 助教 (30740237)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 記憶・学習 / 感覚入力 / 神経ネットワーク / 認知機能 / 記憶痕跡回路 / DREADD / 恐怖条件付け / 認知症モデル

Outline of Research at the Start

感覚入力を受けたときにマウス脳内で反応する神経細胞群の記憶保持機構における役割を明らかにするため、神経活動操作実験および記憶痕跡回路での神経活動イメージング解析を行う。恐怖条件付け学習などの記憶タスクにより、脳内で神経活動に応答した記憶痕跡回路が形成される。感覚刺激により大脳皮質で特異的に応答する神経細胞群を同定し、その細胞群が記憶痕跡回路形成に寄与するのかどうかを検証し、新規記憶形成メカニズムを提案する。

Outline of Final Research Achievements

Fear conditioning is one of the learning tasks, in which sensory stimuli such as novel environment exposures and electric foot shock are combined in the brain to organize fear memories of the sensory stimuli. As a result, fear memories are recalled even when sensory stimuli are presented alone. For the memory formation, a memory trace is organized in the brain by changing the neuronal network. In this research project, we succeeded in identifying a group of sensory-processing neurons that play an important role in the formation of memory traces revealed by wide-field neural activity imaging and neural activity manipulation experiments.

Academic Significance and Societal Importance of the Research Achievements

種々の感覚刺激が脳内で統合され、記憶痕跡回路が脳内で形成されることで感覚刺激の提示に対する反応性が変化します。本研究では広域の神経活動イメージングを実施することにより、この感覚統合に重要な役割を果たす脳内の新規神経細胞群を特定することに成功しました。それにより感覚統合および記憶形成の新規メカニズムを提唱することが可能となりました。また認知症など認知機能が低下する場面での病態メカニズムに対する新たな視点を与える可能性を有しています。

Research Products

• [Journal Article] Imaging neural circuit pathology of autism spectrum disorders: autism-associated genes, animal models and the application of <i>in vivo</i> two-photon imaging (2022)
  • Author(s): Terashima Hiroshi、Minatohara Keiichiro、Maruoka Hisato、Okabe Shigeo
  • Journal Title: Microscopy Volume: 71 Issue: Supplement_1 Pages: i81-i99
  • DOI: 10.1093/jmicro/dfab039
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neurodegenerative processes accelerated by protein malnutrition and decelerated by essential amino acids in a tauopathy mouse model (2021)
  • Author(s): Sato H、Takado Y、Toyoda S、Tsukamoto-Yasui M、Minatohara K、Takuwa H、Urushihata T、Takahashi M、Shimojo M、Ono M、Maeda J、Orihara A、Sahara N、Aoki I、Karakawa S、Isokawa M、Kawasaki N、Kawasaki M、Ueno S、Kanda M、Nishimura M、Suzuki K、Mitsui A、Nagao K、Kitamura A、Higuchi M
  • Journal Title: Science Advances Volume: 7 Issue: 43 Pages: 1-11
  • DOI: 10.1126/sciadv.abd5046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selective Disruption of Inhibitory Synapses Leading to Neuronal Hyperexcitability at an Early Stage of Tau Pathogenesis in a Mouse Model. (2020)
  • Author(s): Shimojo M, Takuwa H, Takado Y, Tokunaga M, Tsukamoto S, Minatohara K, Ono M, Seki C, Maeda J, Urushihata T, Minamihisamatsu T, Aoki I, Kawamura K, Zhang MR, Suhara T, Sahara N, Higuchi M.
  • Journal Title: J Neurosci. Volume: 40 Issue: 17 Pages: 3491-3501
  • DOI: 10.1523/jneurosci.2880-19.2020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Fear memory recall facilitates spine formation in the activated neurons inducing the immediate- early gene Arc in the mouse hippocampus (2022)
  • Author(s): Keiichiro Minatohara, Haruhiko Bito, Shigeo Okabe, Hiroyuki Okuno
  • Organizer: 第127回日本解剖学会総会・全国学術集会
• [Presentation] Association of a neutral contextual memory with a fearful experience induces synapse formation selectively in Arc-expressing neurons of the mouse retrosplenial cortex (2021)
  • Author(s): K. MINATOHARA, S. OHNAMI, S. OKABE, H. BITO, H. OKUNO
  • Organizer: SfN Global Connectome
  • Int'l Joint Research