Physiological mechanism of sequential firing of hippocampal neurons during SW-R

• Project/Area Number: 17H07086
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Keio University
• Principal Investigator: Ishikawa Tomoe 慶應義塾大学, 医学部(信濃町), 助教 (20804587)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: sharp waves/ripples / シナプス入力 / スパイン / シークエンス入力 / 海馬 / クラスター入力 / 樹状突起スパイン / 記憶再生 / 機能的スパインイメージング / 海馬CA1野神経細胞 / 記憶の再生 / 海馬CA1野 / 大規模スパインカルシウムイメージング / SW-R

Outline of Final Research Achievements

Sequential reactivation of memory-relevant neuron ensembles during hippocampal sharp-wave ripple (SW-R) oscillations reflects cognitive processing. However, how a downstream neuron decodes this spatiotemporally organized activity remains unexplored. Using subcellular calcium imaging from CA1 pyramidal neurons in ex vivo hippocampal networks, we discovered that neighboring spines are activated serially along dendrites toward or away from the cell bodies. The sequential spine activity was engaged repeatedly in different SW-Rs in a complex manner. In a single SW-R event, multiple sequences appeared discretely in dendritic trees, but as a whole, sequences occurred preferentially in some dendritic branches. Thus, sequential replays of multineuronal spikes are distributed across several compartmentalized dendritic foci of a postsynaptic neuron with their spatiotemporal features preserved.

Academic Significance and Societal Importance of the Research Achievements

本研究では、SW-Rに参加するか否かを明確に分け、シナプス入力の時空間パターンを比較し、SW-Rに参加する細胞は近接したスパインが繰り返しシークエンス入力を受け取ることを見出した。この結果は、記憶再生時の細胞選択的な発火メカニズムに「シークエンス構造をもつシナプス入力」が関与しうること示唆した点で意義深い。また、シークエンス入力の存在を初めて捉えた知見でもあり、今後、樹状突起の演算様式のより詳細な解明につなが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] GABAergic inhibition reduces the impact of synaptic excitation on somatic excitation (2018)
  • Author(s): Kobayashi Chiaki、Okamoto Kazuki、Mochizuki Yasuhiro、Urakubo Hidetoshi、Funayama Kenta、Ishikawa Tomoe、Kashima Tetsuhiko、Ouchi Ayako、Szymanska Agnieszka F.、Ishii Shin、Ikegaya Yuji
  • Journal Title: Neuroscience Research Volume: - Pages: 00-00
  • DOI: 10.1016/j.neures.2018.09.014
  • Peer Reviewed
• [Journal Article] Hippocampal ripples down-regulate synapses (2018)
  • Author(s): Norimoto Hiroaki、Makino Kenichi、Gao Mengxuan、Shikano Yu、Okamoto Kazuki、Ishikawa Tomoe、Sasaki Takuya、Hioki Hiroyuki、Fujisawa Shigeyoshi、Ikegaya Yuji
  • Journal Title: Science Volume: 359 Issue: 6383 Pages: 1524-1527
  • DOI: 10.1126/science.aao0702
  • Peer Reviewed
• [Presentation] 髄膜リンパ管が脳機能に与える影響の解明 (2019)
  • Author(s): 松岡将司、満倉靖恵、石川智愛、安井正人
  • Organizer: 第92回日本薬理学会年会
• [Presentation] Water intoxication induces systemic reactions, including closure of paravascular space, in vivo. (2018)
  • Author(s): Ishikawa, T., Unekawa, M., Tomita, Y., Nakahara, J., Yasui, M.
  • Organizer: 6th International Conference on Glial Biology in Medicine
  • Int'l Joint Research
• [Presentation] Real-time in vivo observation of the volume changes in astrocytes and perivascular spaces during water intoxication. (2018)
  • Author(s): Ishikawa, T., Unekawa, M., Tomita, Y., Yasui, M.
  • Organizer: 11th FENS Forum of Neuroscience
  • Int'l Joint Research
• [Presentation] 水中毒が全身の生理パラメータおよびparavascular spaceに与える影響 (2018)
  • Author(s): 石川智愛、畝川美悠紀、冨田裕、中原仁、安井正人
  • Organizer: 先端モデル動物支援プラットフォーム若手支援技術講習会2018
• [Presentation] CA1 pyramidal neurons receive spatially clustered synaptic inputs during sharp waves/ripples EX vivo (2017)
  • Author(s): Ishikawa, T., Ikegaya, Y.
  • Organizer: Society for 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): Nomura, H., Mizuta, H., Norimoto, H., Masuda, F., Miura, Y., Kojima, H., Ashizuka, A., Matsukawa, N., Baraki, Z., Hitora-Imamura, N., Nakayama, D., Ishikawa, T., Saito, R., Sano, Y., Kusuhara, H., Minami, M., Takahashi, H., Ikegaya, Y.
  • Organizer: Society for Neuroscience 2017
  • Int'l Joint Research
• [Presentation] Sharp Wave発生時における空間的に局在したシナプス入力 (2017)
  • Author(s): 石川智愛、池谷裕二
  • Organizer: 第40回日本神経科学大会
• [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