Establishment of a new technique for time lapse imaging of activity pattern of engram cells from pre- to post-learning phase

• Project/Area Number: 26640008
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: University of Toyama
• Principal Investigator: OHKAWA Noriaki 富山大学, 大学院医学薬学研究部(医学), 講師 (80416651)
• Co-Investigator(Renkei-kenkyūsha): INOKUCHI Kaoru 富山大学, 大学院医学薬学研究部(医学), 教授 (20318827)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: Ca2+イメージング / 学習 / 記憶 / 記憶痕跡細胞 / 神経活動 / 遺伝子発現 / レンチウイルス / 記憶痕跡

Outline of Final Research Achievements

To identify rules for expression of engram, we proposed to establish a new technique to observe activity pattern of engram cells from pre- to post-learning phase.
We installed a GRIN lens on hippocampal CA1, and a miniature microscope detected fluorescence signals in the CA1 through the GRIN lens. Then we applied the microscopy on transgenic mice in which hippocampal neurons express G-CaMP and engram cells express a fluorescence protein, KikGR. The G-CaMP is a calcium indicator and shows fluorescence when neural activity induces calcium influx into the CA1 neurons. We have succeeded to observe both of engram cells expressing the KikGR and activity-mediated G-CaMP fluorescence of ~400 neurons from freely moving mice with the miniature microscope.
The new technique will allow to investigate comparisons of activity pattern between engram cells and others during memory processing.

Research Products

• [Journal Article] 記憶痕跡とメモリーアロケーション (2016)
  • Author(s): 佐野良威、大川 宜昭、鈴木章円、井ノ口 馨
  • Journal Title: 医学書院・生体の科学 特集：記憶ふたたび Volume: 67 Pages: 22-26
• [Journal Article] Artificial association of pre-stored information to generate a qualitatively new memory (2015)
  • Author(s): Ohkawa N, Saitoh Y, Suzuki A, Tsujimura S, Murayama E, Kosugi S, Nishizono H, Matsuo M, Takahashi Y, Nagase M, Sugimura YK, Watabe AM, Kato F, Inokuchi K
  • Journal Title: Cell Reports Volume: 11 Issue: 2 Pages: 1-9
  • DOI: 10.1016/j.celrep.2015.03.017
  • Peer Reviewed / Open Access
• [Journal Article] Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency stimulation to induce long-term potentiation in the dentate gyrus (2015)
  • Author(s): Nihonmatsu I., Ohkawa N., Saitoh Y. and Inokuchi K.
  • Journal Title: Biology Open Volume: 4 Issue: 11 Pages: 1387-1394
  • DOI: 10.1242/bio.013243
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] オプトジェネティクスによる記憶の操作 (2015)
  • Author(s): 大川宜昭，井ノ口馨
  • Journal Title: 羊土社・実験医学 特集：オプトジェネティクス・細胞・組織・個体を光で操作する Volume: 33 Pages: 3065-3069
• [Presentation] Generating an artificial CS-US associative memory by manipulation of parietal association cortex. (2015)
  • Author(s): Suzuki A., Kosugi-Ushijima S., Ohkawa N., Matsuo M., Nishizono H., and Inokuchi K.
  • Organizer: Neuroscience 2015, Annual Meeting of Society for Neuroscience, 2015.
  • Place of Presentation: Chicago., USA.
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Enhancing memory destabilization through protein degradation induction. (2015)
  • Author(s): Shehata M., Zhao Q., Abdou K., Okubo-Suzuki R., Saitoh Y., Kitamura T., Nishizono H., Matsuo M., Ohkawa N., and Inokuchi K.
  • Organizer: Neuroscience 2015, Annual Meeting of Society for Neuroscience, 2015.
  • Place of Presentation: Chicago., USA.
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Overlapping in two cellular ensembles in the hippocampal CA1 region is important for behavioral tagging. (2015)
  • Author(s): Nomoto M., Ohkawa N., Nishizono H., Matsuo M., Yokose J., Takahashi Y., Nagase M., Suzuki A., Watabe A.M., Kato F., and Inokuchi K.
  • Organizer: Neuroscience 2015, Annual Meeting of Society for Neuroscience, 2015.
  • Place of Presentation: Chicago., USA.
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Synergistic activity during retrieval of neuronal ensembles between two distinct memory traces generates cross-modal linkage. (2015)
  • Author(s): Yokose J., Nomoto M., Okubo-Suzuki R., Ohkawa N., Nishizono H., Matsuo M., Suzuki A., Takahashi Y., Nagase M., Watabe A.M., Kato F., and Inokuchi K.
  • Organizer: Neuroscience 2015, Annual Meeting of Society for Neuroscience, 2015.
  • Place of Presentation: Chicago., USA.
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Adult neurogenesis modulates the hippocampal learning capacity. (2015)
  • Author(s): Alam M., Kitamura T., Saitoh Y., Ohkawa N., Kondo T., and Inokuchi K.
  • Organizer: Neuroscience 2015, Annual Meeting of Society for Neuroscience, 2015.
  • Place of Presentation: Chicago., USA.
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Artificial association of pre-stored information in hippocampus and amygdala． (2015)
  • Author(s): Ohkawa N., Saitoh Y., Suzuki A., Tsujimura S., Murayama E., Kosugi S., Nishizono H., Matsuo M., Takahashi Y., Nagase M., Sugimura Y.K., Watabe A.M., Kato F., Inokuchi K.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Parietal association cortex regulates CS-US association of contextual fear memory. (2015)
  • Author(s): Suzuki A., Kosugi S., Ohkawa N., Nishizono H., Inokuchi K.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Overlapping in two cellular ensembles in the hippocampal CA1 region is required for behavioral tagging. (2015)
  • Author(s): Nomoto M., Yokose J., Takahashi Y., Nagase M., Suzuki A., Ohkawa N., Nishizono H., Watabe A.M., Kato F., Inokuchi K.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Synergistic activity between distinct neuronal ensembles creates the association of memory. (2015)
  • Author(s): Yokose J., Nomoto M., Okubo-Suzuki R., Takahashi Y., Nagase M., Suzuki A., Ohkawa N., Nishizono H., Watabe A.M., Kato F., Inokuchi K.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Adult neurogenesis modulates the hippocampal learning capacity. (2015)
  • Author(s): Jahangir A.M., Kitamura T., Saitoh Y., Ohkawa N., Kondo T., Inokuchi K.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Automatic detection system of cell shape and spike timing for calcium imaging data using iterative sequential quadratic programing． (2015)
  • Author(s): Takekawa T., Sato M., Ohkawa N., Inokuchi K., Hayashi Y., Fukai T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Artificial association of information residing in hippocampus and amygdala. (2014)
  • Author(s): Ohkawa N., Saitoh Y., Suzuki A., Tsujimura S., Murayama E., Nishizono H., Matsuo M., Takahashi Y., Nagase M., Sugimura Y.K., Watabe A.M., Kato F., and Inokuchi K.
  • Organizer: Neuroscience 2014, Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington, D.C.
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Artificial association of information residing in hippocampus and amygdala. (2014)
  • Author(s): Ohkawa N., Saitoh Y., Suzuki A., Tsujimura S., Murayama E., Nishizono H., Matsuo M., Takahashi Y., Nagase M., Sugimura Y.K., Watabe A.M., Kato F., and Inokuchi K.
  • Organizer: 13th Annual MCCS meeting in Washington, D.C.
  • Place of Presentation: Washington, D.C.
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] 異なるセルアンサンブルの光遺伝学的活性化による連合記憶の人工的創出． (2014)
  • Author(s): 大川宜昭，斎藤喜人，鈴木章円，辻村周平，村山絵美，西園啓文，松尾美奈，高橋由香里，長瀬将志，杉村弥恵，渡部文子，加藤総夫，井ノ口馨
  • Organizer: 第37回日本神経科学大会大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Book] 記憶のダイナミクスとそのメカニズム，リハビリテーションのためのニューロサイエンス 脳科学からみる機能回復 (2015)
  • Author(s): 大川 宜昭, 浦川 将
  • Total Pages: 279
  • Publisher: メジカルビュー社
• [Remarks] 富山大学大学院医学薬学研究部（医学）生化学講座
  • URL: http://www.med.u-toyama.ac.jp/bmb/index-j.html
• [Remarks] 共同発表：異なる古い記憶を人為的に組み合わせ、新しい記憶を作り出すことに成功・JST・富山大学
  • URL: http://www.jst.go.jp/pr/announce/20150403/
• [Remarks] DEPARTMENT OF BIOCHEMISTRY INOKUCHI LAB.
  • URL: http://www.med.u-toyama.ac.jp/bmb/index-j.html