Neural circuit for enhancing memory retrieval

• Project/Area Number: 16K06989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Hokkaido University
• Principal Investigator: Nomura Hiroshi 北海道大学, 薬学研究院, 講師 (10549603)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 記憶 / 脳 / 脳・神経 / 神経科学

Outline of Final Research Achievements

Forgotten memories may occasionally be recollected spontaneously. Even after the memories fade over time, the forgotten memories may persist latently in the brain. However, clinically applicable method that promotes the retrieval of forgotten long-term memories has not yet been established.
In the current study, we examined whether activation of brain histamine system promote the retrieval of a forgotten long-term object memory in mice. We employed the novel object recognition task, in which the test session mice were presented with a novel object and a familiar object that was presented during the training session. One week after training, the mice were unable to discriminate the novel object from the familiar one. However, activation of brain histamine system before the test session enhanced discrimination score. The results indicate that activation of brain histamine system promotes retrieval of forgotten object memories.

Academic Significance and Societal Importance of the Research Achievements

脳内ヒスタミン神経系の活性化によって記憶の想起が改善するという本研究の成果は、脳内ヒスタミンの働きやヒスタミン活性化薬の作用だけでなく、柔軟に働く記憶のメカニズムの解明に貢献する。さらにアルツハイマー病などの認知機能障害の治療薬開発の一助となることが期待される。

Research Products

• [Journal Article] Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories (2019)
  • Author(s): Nomura H, Mizuta H, Norimoto H, Masuda F, Miura Y, Kubo A, Kojima H, Ashizuka A, Matsukawa N, Baraki Z, Hitora-Imamura N, Nakayama D, Ishikawa T, Okada M, Orita K, Saito R, Yamauchi N, Sano Y, Kusuhara H, Minami M, Takahashi H, Ikegaya Y
  • Journal Title: Biological Psychiatry Volume: 印刷中 Issue: 3 Pages: 230-239
  • DOI: 10.1016/j.biopsych.2018.11.009
  • NAID: 120006876277
  • Peer Reviewed
• [Journal Article] Prior observation of fear learning enhances subsequent self-experienced fear learning with an overlapping neuronal ensemble in the dorsal hippocampus (2019)
  • Author(s): Nomura Hiroshi、Teshirogi Chie、Nakayama Daisuke、Minami Masabumi、Ikegaya Yuji
  • Journal Title: Molecular Brain Volume: 12 Issue: 1 Pages: 21-21
  • DOI: 10.1186/s13041-019-0443-6
  • NAID: 120006620601
  • Peer Reviewed / Open Access
• [Presentation] ヒスタミン神経系の活性化による物体認識記憶の回復 (2018)
  • Author(s): 久保絢女、大森翔平、南雅文、野村洋
  • Organizer: 日本薬学会北海道支部第145回例会
• [Presentation] Brain histamine boosts reactivation of weak memory engrams and restores forgotten long-term memories in mice and humans (2018)
  • Author(s): Hiroshi Nomura, Hiroto Mizuta, Hiroaki Norimoto, Fumitaka Masuda, Yuki Miura, Hiroto Kojima, Aoi Ahizuka, Noriko Matsukawa, Zohal Baraki, Natsuko Hitora-Imamura, Daisuke Nakayama, Tomoe Ishikawa, Mami Okada, Ryoki Saito, Ayame Kubo, Yamato Sano, Hiroyuki Kusuhara, Masabumi Minami, Hidehiko Takahashi, Yuji Ikegaya
  • Organizer: WCP2018
  • Int'l Joint Research
• [Presentation] Histamine enhances reactivation of weak memory engrams and restores forgotten long-term memories (2018)
  • Author(s): Hiroshi Nomura, Hiroto Mizuta, Hiroaki Norimoto, Fumitaka Masuda, Yuki Miura, Hiroto Kojima, Aoi Ahizuka, Noriko Matsukawa, Zohal Baraki, Natsuko Hitora-Imamura, Daisuke Nakayama, Tomoe Ishikawa, Mami Okada, Ryoki Saito, Ayame Kubo, Yamato Sano, Hiroyuki Kusuhara, Masabumi Minami, Hidehiko Takahashi, Yuji Ikegaya
  • Organizer: GRC, Optogenetics and Imaging: Technology Development, Novel Applications, and Closing the Loop Between Models and Experiments
  • Int'l Joint Research
• [Presentation] ヒスタミン神経系の操作による記憶の回復 (2018)
  • Author(s): 野村洋
  • Organizer: 平成30年度生理研研究会 『記憶研究会』
  • Invited
• [Presentation] Central histamine modulates learning and memory (2018)
  • Author(s): Hiroshi Nomura
  • Organizer: 第92年会日本薬理学会年会
• [Presentation] Brain histamine promotes memory retrieval (2018)
  • Author(s): Hiroshi Nomura, Ayame Kubo, Hiroto Kojima, Shohei Ohmori, Kyoka Nishimura, Yuji Ikegaya, Masabumi Minami
  • Organizer: 第92年会日本薬理学会年会
• [Presentation] Central histamine reactivates weak memory engrams and restores forgotten memories (2018)
  • Author(s): Hiroshi Nomura
  • Organizer: 脳と心のメカニズム 第18回冬のワークショップ
  • Invited
• [Presentation] Reward seeking by neuronal silencing in the auditory cortex (2017)
  • Author(s): Hiroshi Nomura, Kojiro Hara, Reimi Abe, Natsuko Hitora-Imamura, Ryota Nakayama, Takuya Sasaki, Norio Matsuki, Yuji Ikegaya, Masabumi Minami
  • Organizer: 内藤コンファレンス
• [Presentation] Central histamine reactivates weak memory engrams and restores apparently forgotten object memories in mice and humans (2017)
  • Author(s): Hiroshi Nomura, Hiroto Mizuta, Hiroaki Norimoto, Fumitaka Masuda, Yuki Miura, Hiroto Kojima, Aoi Ashizuka, Noriko Matsukawa, Zohal Baraki, Natsuko Hitora-Imamura, Daisuke Nakayama, Tomoe Ishikawa, Ryoki Saito, Yamato Sano, Hiroyuki Kusuhara, Masabumi Minami, Hidehiko Takahashi, Yuji Ikegaya
  • Organizer: Neuroscience 2017
  • Int'l Joint Research
• [Presentation] Central histamine reactivates weak memory engrams and restores apparently forgotten object memories in mice and humans (2017)
  • Author(s): Hiroshi Nomura, Hiroto Mizuta, Hiroaki Norimoto, Fumitaka Masuda, Yuki Miura, Hiroto Kojima, Aoi Ashizuka, Noriko Matsukawa, Zohal Baraki, Natsuko Hitora-Imamura, Daisuke Nakayama, Tomoe Ishikawa, Ryoki Saito, Yamato Sano, Hiroyuki Kusuhara, Masabumi Minami, Hidehiko Takahashi, Yuji Ikegaya
  • Organizer: 16th Annual MCCS Symposium
  • Int'l Joint Research
• [Presentation] ヒスタミンH3受容体逆アゴニストは、思い出せなくなった物体記憶を回復させる (2017)
  • Author(s): 野村洋、水田弘人、乘本裕明、増田文貴、三浦友樹、小島寛人、芦塚あおい、松河理子、Zohal Baraki、人羅（今村）菜津子、中山大輔、石川智愛、齋藤瞭毅、佐野大和、楠原洋之、南雅文、高橋英彦、池谷裕二
  • Organizer: 第39回日本生物学的精神医学会・第47回日本神経精神薬理学会 合同年会
• [Presentation] Histamine H3 receptor inverse agonists restore apparently forgotten memories (2017)
  • Author(s): Hiroshi Nomura, Hiroaki Norimoto, Fumitaka Masuda, Yuki Miura, Hiroto Kojima, Zohal Baraki, Natsuko Hitora-Imamura, Daisuke Nakayama, Tomoe Ishikawa, Ryoki Saito, Yamato Sano, Hiroyuki Kusuhara, Masabumi Minami, Yuji Ikegaya
  • Organizer: 第40回神経科学大会
• [Presentation] Neuronal circuits for learning and memory (2016)
  • Author(s): Hiroshi Nomura
  • Organizer: The 2nd HU-TMU- KU Joint Symposium for Pharmaceutical Sciences
  • Place of Presentation: 台北（台湾）
  • Int'l Joint Research / Invited
• [Presentation] 分界条床核ニューロンによる不安行動の処理機構 (2016)
  • Author(s): 野村洋
  • Organizer: 第8回光操作研究会
  • Place of Presentation: 慶應義塾大学（東京都港区）
  • Invited