Integration of the adult-born neurons into memory circuits during sleep

• Project/Area Number: 15F15408
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 外国
• Research Field: Basic / Social brain science
• Research Institution: University of Tsukuba
• Principal Investigator: 坂口 昌徳 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (60407088)
• Co-Investigator(Kenkyū-buntansha): KUMAR DEEPENDRA 筑波大学, 国際統合睡眠医科学研究機構, 外国人特別研究員
• Project Period (FY): 2015-11-09 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,300,000 (Direct Cost: ¥2,300,000); Fiscal Year 2017: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2016: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2015: ¥400,000 (Direct Cost: ¥400,000)
• Keywords: 記憶 / 新生ニューロン / 睡眠 / 恐怖記憶

Outline of Annual Research Achievements

ほ乳類の成体脳では、稀な例外を除きニューロンは新生しない。この例外的現象が起こる場所として、ヒトを含む成体海馬内に存在する歯状回という組織がある。歯状回では神経幹細胞からニューロンの新生が生涯続く。この新生ニューロンを上手く利用することで再生医療に応用されることが期待されている(Akers and Sakaguchi* et al., Stem Cells, 2018　Feb)。新生ニューロンは成熟にともない、既存の神経回路に組込まれながら協調して機能回路を形作ると考えられている。これは細胞の数自体の増減を想定していない既存の記憶メカニズム概念とは大きく異なる可能性がある(Aimone and Gage, Neuron, 2011, v33, p1160)。今回我々は、光遺伝学の技術を用い、新生してからの期間が一定(例えば生まれてから4週後)のニューロンを、特定の睡眠期に焦点を当て、その興奮制御が可能なシステムを開発した。このシステムはリアルタイムで睡眠を判定しながら、新生ニューロンの興奮だけを一過性に高い時間分解能で制御できる点で画期的である。そしてこのシステムを用い、特定の発生期にある新生ニューロンの睡眠中の興奮が、恐怖記憶の固定化に必要であることを見出した。また予想したとおり、睡眠中に新生ニューロンが海馬非依存性の記憶に果たす役割は大きくないことも見出された。これは新生ニューロンの睡眠との機能的相関関係を示した初めての研究であり、今後このメカニズムを詳細に解析することで、ヒト脳がもつニューロンの新生を利用した再生医療への応用へ貢献できると考えられる。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Columbia University/New York University(USA)
• [Int'l Joint Research] Edinburgh University/Oxford University(UK)
• [Int'l Joint Research] KAIST(KOREA)
• [Int'l Joint Research] Columbia Univ./New York Univ.(米国)
• [Int'l Joint Research] University of Edinburgh(英国)
• [Int'l Joint Research] University of Toronto(Canada)
• [Int'l Joint Research] MIT Media lab(米国)
• [Journal Article] Concise Review: Regulatory Influence of Sleep and Epigenetics on Adult Hippocampal Neurogenesis and Cognitive and Emotional Function (2018)
  • Author(s): Akers Katherine G.、Cherasse Yoan、Fujita Yuki、Srinivasan Sakthivel、Sakurai Takeshi、Sakaguchi Masanori
  • Journal Title: Stem Cells Volume: - Issue: 7 Pages: 969-976
  • DOI: 10.1002/stem.2815
  • NAID: 120007133829
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Auditory conditioned stimulus presentation during NREM sleep impairs fear memory in mice (2017)
  • Author(s): Purple Ross J.、Sakurai Takeshi、Sakaguchi Masanori
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 46247-46247
  • DOI: 10.1038/srep46247
  • NAID: 120007129189
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The importance of acute intervention for preventing generalization in PTSD patients (2016)
  • Author(s): 大石誠, 中島聡美, 坂口昌徳
  • Journal Title: 医学のあゆみ Volume: 25 Pages: 1209-1210
  • Acknowledgement Compliant
• [Journal Article] 脳内で新生するニューロンと中枢神経再生への応用 (2016)
  • Author(s): 坂口 昌徳
  • Journal Title: ブレインサイエンスレビュー, 2016 Volume: なし Pages: 263-279
  • Acknowledgement Compliant
• [Journal Article] Effect of context exposure after fear learning on memory generalization in mice (2016)
  • Author(s): Fujinaka A, Li R, Hayashi M, Kumar D, Changarathil G, Naito K, Miki K, Nishiyama T, Lazarus M, Sakurai S, Kee N, Nakajima S, Wang SH, Sakaguchi M
  • Journal Title: Mol. Brain Volume: 9 Issue: 1 Pages: 1-7
  • DOI: 10.1186/s13041-015-0184-0
  • NAID: 120007128522
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 心的外傷直後の場所刺激が記憶汎化に与える影響 (2016)
  • Author(s): 大石誠、坂口昌徳
  • Journal Title: 医学の歩み Volume: 印刷中
  • Acknowledgement Compliant
• [Journal Article] 脳内で新生するニューロンと中枢神経再生への応用 (2016)
  • Author(s): 坂口 昌徳
  • Journal Title: ブレインサイエンスレビュー2016 Volume: 2016 Pages: 263-279
• [Journal Article] Inhibiting the Activity of CA1 Hippocampal Neurons Prevents the Recall of Contextual Fear Memory in Inducible ArchT Transgenic Mice. (2015)
  • Author(s): Sakaguchi M, Kim K, Yu LM, Hashikawa Y, Sekine Y, Okumura Y, Kawano M, Hayashi M, Kumar D, Boyden ES, McHugh TJ, Hayashi Y.
  • Journal Title: PLoS One. Volume: 10 Issue: 6 Pages: 1-11
  • DOI: 10.1371/journal.pone.0130163
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Memory consolidation during sleep and its mechanism for clinical insights (2018)
  • Author(s): Masanori Sakaguchi
  • Organizer: Asian Society of Sleep Medicine 2018 Cogress
  • Int'l Joint Research / Invited
• [Presentation] Mechanism of memory consolidation during sleep (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: 分子細胞情報学セミナー
  • Invited
• [Presentation] Function of adult-born neurons during sleep (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: 東京医科歯科大学教室セミナー
  • Invited
• [Presentation] Adult-born neurons in memory consolidation during sleep (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: 東北大学 Neuro Global 国際共同大学院プログラム
  • Invited
• [Presentation] Mechanism of memory consolidation during sleep (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: NIPS conference: An approach to the integrative understanding of learning and memory
  • Invited
• [Presentation] 脳と心のフロンティア～「知」と「療」の連携 (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: The 39th Japanese Society for Biological Psychology, The 47th Japanese Society for Neuropsychopharmacology
  • Invited
• [Presentation] The role of adult-born neurons in memory consolidation during sleep (2017)
  • Author(s): Deependra Kumar
  • Organizer: Indian society for sleep research
  • Int'l Joint Research / Invited
• [Presentation] Function of the adult-born neurons for memory consolidation during sleep (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: The 20th KSBNS annual meeting
  • Int'l Joint Research / Invited
• [Presentation] EEG brain rhythms for memory consolidation during sleep (2017)
  • Author(s): Nondhalee Pimpimon
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
  • Int'l Joint Research
• [Presentation] Active Role of Sleep in Forgetting of Memory (2017)
  • Author(s): Ruth Li
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
  • Int'l Joint Research
• [Presentation] Molecular mechanisms of memory consolidation during sleep (2017)
  • Author(s): Iyo Koyanagi
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society
  • Int'l Joint Research
• [Presentation] Function of the adult-born neurons in memory consolidation during sleep (2017)
  • Author(s): Masanori Sakaguchi
  • Organizer: Department seminar, Peking University, Beijing, China
  • Invited
• [Presentation] The role of adult born neurons in memory consolidation during sleep-wake cycles (2016)
  • Author(s): Kumar D, Hayashi M, Hayashi X, Changarathil G, Wintzer M, McHugh TJ, Sakurai T, Yanagisawa M, Sakaguchi M
  • Organizer: Society for Neuroscience
  • Place of Presentation: Convention Center, San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] マウス光遺伝学を用いたトラウマ記憶の脳内処理過程 (2016)
  • Author(s): 坂口 昌徳, Deependra Kumar, 林 政信、大石 誠,
  • Organizer: 医療心理懇話会演題
  • Place of Presentation: フクラシア東京、東京都中央区
  • Year and Date: 2016-11-02
  • Invited
• [Presentation] Function of the adult-born neurons in memory consolidation during sleep, (2016)
  • Author(s): Masanori Sakaguchi, Masanobu Hayashi, Makoto Oishi, Xifang Hayashi, Boran Osman, Sima Singh, Marie Wintzer, Thomas J. McHugh, Takeshi Sakurai, Masashi Yanagisawa, Deependra Kumar
  • Organizer: RIKEN PDFA Pizza and Science Seminars
  • Place of Presentation: RIKEN BSI, 埼玉県和光市
  • Year and Date: 2016-10-19
  • Invited
• [Presentation] Function of the adult-born neurons in memory consolidation during sleep (2016)
  • Author(s): Deependra Kumar, Masanori Sakaguchi
  • Organizer: Memory Meeting 2016
  • Place of Presentation: 東京大学、東京都文京区
  • Year and Date: 2016-07-23
  • Invited
• [Presentation] The vulnerable period for a fear memory consolidation revealed by sleep deprivation (2016)
  • Author(s): Ruoshi Li, Takeshi Sakurai, Masanori Sakaguchi
  • Organizer: 第３９回日本神経科学会大会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2016-07-21
  • Int'l Joint Research
• [Presentation] Effect of context exposure after fear learning on memory generalization in mice (2016)
  • Author(s): Li R, Fujinaka A, Hayashi M, Kumar D, Changarathil G, Naito K, Miki K, Nishiyama T, Lazarus M, Sakurai T, Kee N, Nakajima S, Wang SH, Sakaguchi M
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜, 神奈川県横浜市
  • Year and Date: 2016-07-20
• [Presentation] 成体脳で新生するニューロンが、睡眠中の記憶の固定化に果たす役割り (2016)
  • Author(s): 坂口昌徳, Deependra Kumar, 林政信, 林細芳, Gopakumar Changarathil, Marie Wintzer, Thomas J. McHugh, 櫻井武, 柳沢正史
  • Organizer: 日本睡眠学会第41回定期学術集会
  • Place of Presentation: 京王プラザホテル、東京都新宿区
  • Year and Date: 2016-07-08
  • Invited
• [Presentation] The activity of adult born neurons are necessary for memory consolidation during sleep (2016)
  • Author(s): Sakaguchi M, Kumar D, Hayashi M, Hayashi X, Changarathil G, Singh S, Wintzer M, McHugh TJ, Sakurai T, Yanagisawa M
  • Organizer: NCTC seminar
  • Place of Presentation: National Chiao-Tung Univ, Hsinchu, Taiwan
  • Year and Date: 2016-05-26
  • Invited
• [Presentation] The activity of adult born neurons are necessary for memory consolidation during sleep (2016)
  • Author(s): Kumar D, Hayashi M, Hayashi X, Changarathil G, Singh S, Wintzer M, McHugh TJ, Sakurai T, Yanagisawa M, Sakaguchi M
  • Organizer: NCTC seminar
  • Place of Presentation: National Chiao-Tung University, Hsinchu(Taiwan)
  • Year and Date: 2016-05-26
  • Int'l Joint Research / Invited
• [Presentation] 新生ニューロンの光制御にて明らかにする記憶と睡眠の関係 (2016)
  • Author(s): 坂口昌徳, Deependra Kumar, 林政信, 林Xifang, Gopakumar Changarathil, 櫻井武
  • Organizer: 第８９回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜, 神奈川県横浜市
  • Year and Date: 2016-03-10
  • Invited
• [Presentation] Adult neurogenesis plays critical role in sleep stage dependent memory formation (2016)
  • Author(s): 坂口昌徳
  • Organizer: 金沢大学 脳肝センターシンポジウム
  • Place of Presentation: 全日空ホテル, 石川県金沢市
  • Year and Date: 2016-03-07
  • Invited
• [Presentation] The role of adult born neurons in memory consolidation during sleep-wake cycles (2016)
  • Author(s): Kumar D
  • Organizer: The 4th annual IIIS symposium
  • Place of Presentation: EPOCAL Tsukuba, Tsukuba, Ibaraki
  • Year and Date: 2016-02-26
  • Int'l Joint Research / Invited
• [Presentation] Erasing bad memories during sleep (2016)
  • Author(s): Kumar D
  • Organizer: Science Dialogue in Takezono High School
  • Place of Presentation: つくば市竹園高校, 茨城県つくば市
  • Year and Date: 2016-02-24
  • Invited
• [Presentation] Identification of brainstem neurons that play critical roles in sleep/wake and REM/NREM sleep regulation (2015)
  • Author(s): Kashiwagi M, Kanuka M, Sakaguchi M, Itohara S, Hayashi Y
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド, 兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] 睡眠中の新生ニューロンの興奮は、記憶形成に必要である (2015)
  • Author(s): 坂口昌徳
  • Organizer: 第11回成体脳のニューロン新生懇談会
  • Place of Presentation: 名古屋市立大学, 愛知県名古屋市
  • Year and Date: 2015-11-14
• [Presentation] 成体脳に新生するニューロンの光制御により明らかにする,睡眠中の記憶形成機構 (2015)
  • Author(s): 坂口昌徳
  • Organizer: 比較記憶研究会
  • Place of Presentation: 生理学研究所, 愛知県岡崎市
  • Year and Date: 2015-10-09
  • Invited
• [Presentation] 脳の再生 (2015)
  • Author(s): 坂口昌徳
  • Organizer: 慶応義塾大学眼科学教室セミナー
  • Place of Presentation: 慶応義塾大学, 東京都新宿区
  • Year and Date: 2015-09-03
  • Invited
• [Presentation] The function of adult born neurons during sleep (2015)
  • Author(s): Sakaguchi M, Kumar D, Hayashi M, Sakurai T
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場, 兵庫県神戸市
  • Year and Date: 2015-07-29
  • Invited
• [Presentation] 光による脳の再生 (2015)
  • Author(s): Sakaguchi M, Kumar D, Hayashi M, Sakurai T
  • Organizer: 第１回セレンディピティー創出研究会
  • Place of Presentation: 産業技術研究所, 茨城県つくば市
  • Year and Date: 2015-04-23
  • Invited
• [Remarks] Sakurai and Sakaguchi Laboratory Sakaguchi Group
  • URL: http://sakurai-sakaguchi.wpi-iiis.tsukuba.ac.jp/
• [Remarks] トラウマ記憶を弱めるには; マウスの記憶・睡眠研究から考えるPTSDケア
  • URL: https://academist-cf.com/journal/?p=5352
• [Remarks] 睡眠中にPTSDケア —トラウマ記憶を音で消す
  • URL: http://wpi-iiis.tsukuba.ac.jp/japanese/press/1048
• [Remarks] Publication list
  • URL: http://sakurai-sakaguchi.wpi-iiis.tsukuba.ac.jp/publications.html
• [Remarks] sakurai-sakaguchi lab homepage
  • URL: http://sakurai-sakaguchi.wpi-iiis.tsukuba.ac.jp/