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2012 Fiscal Year Annual Research Report

光遺伝学と磁気共鳴機能画像法の融合による大脳記憶機構の解明

Research Project

Project/Area Number 24220008
Research Category

Grant-in-Aid for Scientific Research (S)

Research InstitutionThe University of Tokyo

Principal Investigator

宮下 保司  東京大学, 医学(系)研究科(研究院), 教授 (40114673)

Project Period (FY) 2012-05-31 – 2017-03-31
Keywords磁気共鳴画像法 / 光遺伝学 / 大域的大脳ネットワーク / 記憶システム
Research Abstract

研究は順調に進捗している。本年度の研究実績に概要は以下の通りである。まず、記憶課題遂行中のサル大脳ネットワークの解析において、最初の大きな進捗が得られた(Miyamoto et al., Neuron 77, 787-799, 2013 同誌 SPOTLIGHTに掲載)。この研究では、マカクザルにヒトと同様の認知記憶課題を課し、磁気共鳴画像装置(MRI)内で課題遂行中の脳活動を記録してヒトと比較した。サルでもヒトでも、正しく記憶を想起した時に後部頭頂葉の活動が上昇することが明らかになった。さらに、サル後部頭頂葉に同定された2つの活動領域は、機能的にも解剖学的にも分化していて,それぞれヒトの頭頂葉の細胞構築学的には異なる領域に対応していることが示された。また、サル大脳への神経回路特異的な光遺伝学的刺激法/抑制法の確立に向けて、慢性サル行動課題実験用の新しいoptorodeの開発に成功した(Tamura et al., J. Neurosci. Methods 211, 49-57, 2012)。この新しいoptorodeの有用性は既に国際的に認められており、国際一流誌においての引用も増えつつある(Gerits et al., Trends Genetics 29, 403-411, 2013)。その他、サル大脳への神経回路解析においては、1つの図形を手がかりにして、事前に対として記憶している別の図形を連想する作業を遂行中のサルの側頭葉で、手がかり図形に応答しその情報を保持するニューロン(手がかり図形保持ニューロン)から、別の図形を思い出す時に活動するニューロン(対図形想起ニューロン)へと特異的に神経信号が伝達し、それがさらに他の対図形想起ニューロンへと伝播していくことによって、記憶想起信号が生成され、増幅されることを明らかにした(Hirabayashi et al. Neuron 77, 192-203, 2013 同誌 SPOTLIGHTに掲載)。

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

本研究は、上記「研究実績の概要」に記したように、すでに重要な発見に到達しており、また、今後の研究進展に必要なoptorodeの開発に成功している。その点で、研究は全体としては当初の計画以上に進捗していると評価される。その中で、サル大脳においてChR2等の遺伝子を発現させる実験は、組織障害性の問題が明らかになった為にラットを用いた予備実験に戻って原因等を検討することにした。その為に、研究費の一部を繰り越して使用することとした。この繰越計画に従って行った実験を追加することによって、サル大脳皮質における遺伝子の発現が、ラット大脳皮質における発現と異なること、ならびにこの差異の発生の仕方が遺伝子導入に用いるプロモーターによって異なることが明らかになり、論文発表した(Yaguchi et al., Characterization of the Properties of Seven Promoters in the Motor Cortex of Rats and Monkeys after Lentiviral Vector-Mediated Gene Transfer. Human Gene Therapy Methods 24, 333-344, 2013)。これは今後、本研究を推進する基礎となる重要な進捗であると評価している。

Strategy for Future Research Activity

基本的に、研究計画の変更は無い。当初の研究計画調書記載の計画に従って研究を推進する。

  • Research Products

    (26 results)

All 2013 2012 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] Characterization of the Properties of Seven Promoters in the Motor Cortex of Rats and Monkeys after Lentiviral Vector-Mediated Gene Transfer.2013

    • Author(s)
      Yaguchi M, Ohashi Y, Tsubota T, Sato A., Koyano WK, Wang N, Miyashita Y.
    • Journal Title

      Hum. Gene Ther. Methods

      Volume: 24 Pages: 333–344

    • DOI

      10.1089/hgtb.2012.238

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional differentiation of memory retrieval network in macaque posterior parietal cortex.2013

    • Author(s)
      Miyamoto, K., Osada, T., Adachi, Y., Matsui, T., Kimura, H.M. and Miyashita, Y.
    • Journal Title

      Neuron

      Volume: 77 Pages: 787-799

    • DOI

      10.1016/j.neuron.2012.12.019

    • Peer Reviewed
  • [Journal Article] Functional micro-circuit recruited during retrieval of object association memory in monkey perirhinal cortex.2013

    • Author(s)
      Hirabayashi, T., Takeuchi, D. and Tamura, K. and Miyashita, Y.
    • Journal Title

      Neuron

      Volume: 77 Pages: 192-203

    • DOI

      10.1016/j.neuron.2012.10.031

    • Peer Reviewed
  • [Journal Article] FoxP2 is a parvocellular-specific transcription factor in the visual thalamus of monkeys and ferrets.2013

    • Author(s)
      Iwai, L., Ohashi, Y., van der List, D., Usrey, W.M., Miyashita, Y. and Kawasaki, H.
    • Journal Title

      Cereb. Cortex

      Volume: 23 Pages: 2204-2212

    • DOI

      10.1093/cercor/bhs207

    • Peer Reviewed
  • [Journal Article] Bidirectional effects on inter-hemispheric resting-state functional connectivity induced by excitatory and inhibitory repetitive transcranial magnetic stimulation.2013

    • Author(s)
      Watanabe T, Abe O, Kuwabara H, Yahata N, Takano Y, Iwashiro N, Natsubori T, Aoki Y, Takao H, Kawakubo Y, Kamio Y, Kato N, Miyashita Y, Kasai K, and Yamasue H.
    • Journal Title

      Human Brain Mapping

      Volume: 35 Pages: 1896-1905

    • DOI

      10.1002/hbm.22300, 2013

    • Peer Reviewed
  • [Journal Article] Functional Connectivity between Anatomically Unconnected Areas Is Shaped by Collective Network-level Effects in the Macaque Cortex.2012

    • Author(s)
      Adachi, Y., Osada, T., Sporns, O., Watanabe, T., Matsui, T., Miyamoto, K. and Miyashita, Y.
    • Journal Title

      Cereb. Cortex

      Volume: 22 Pages: 1586-1592

    • DOI

      10.1093/cercor/bhr234

    • Peer Reviewed
  • [Journal Article] Optogenetic inhibition of Purkinje cell activity reveals cerebellar control of blood pressure during postural alterations in anesthetized rats.2012

    • Author(s)
      Tsubota, T., Ohashi, Y., Tamura, K. and Miyashita, Y.
    • Journal Title

      Neuroscience

      Volume: 210 Pages: 137-144

    • DOI

      10.1016/j.neuroscience.2012.03.014

    • Peer Reviewed
  • [Journal Article] Functional Dissociation between Anterior and Posterior Temporal Cortical Regions during Retrieval of Remote Memory.2012

    • Author(s)
      Watanabe, T., Kimura, H. M., Hirose, S., Wada, H., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y. and Konishi, K.
    • Journal Title

      J. Neurosci.

      Volume: 32 Pages: 9659-9670

    • DOI

      10.1523/JNEUROSCI.5553-11.2012

    • Peer Reviewed
  • [Journal Article] Local Signal Time-Series during Rest Used for Areal Boundary Mapping in Individual Human Brains.2012

    • Author(s)
      Hirose, S., Watanabe, T., Jimura, K., Katsura, M., Kunimatsu, A., Abe, O., Ohtomo, K., Miyashita, Y. and Konishi, S.
    • Journal Title

      PLoS One

      Volume: 7 Pages: e36496

    • DOI

      10.1371/journal.pone.0036496

    • Peer Reviewed
  • [Journal Article] Efficiency of Go/No-Go Task Performance Implemented in the Left Hemisphere.2012

    • Author(s)
      Hirose, S., Chikazoe, J., Watanabe, T., Jimura, K., Kunimatsu, A., Abe, O., Ohtomo, K., Miyashita, Y. and Konishi, S.
    • Journal Title

      J. Neurosci.

      Volume: 32 Pages: 9059-9065

    • DOI

      10.1523/JNEUROSCI.0540-12.2012

    • Peer Reviewed
  • [Journal Article] Neurodynamics of Cognitive Set Shifting in Monkey Frontal Cortex and Its Causal Impact on Behavioral Flexibility.2012

    • Author(s)
      Kamigaki, T., Fukushima, T., Tamura, K. and Miyashita, Y.
    • Journal Title

      J. Cogn. Neurosci.

      Volume: 24 Pages: 2171-2185

    • DOI

      10.1162/jocn_a_00277

    • Peer Reviewed
  • [Journal Article] Diminished medial prefrontal activity behind autistic social judgments of incongruent information.2012

    • Author(s)
      Watanabe, T., Yahata, N., Abe, O., Kuwabara, H., Inoue, H., Takano, Y., Iwashiro, N., Natsubori, T., Aoki, Y., Takao, H., Sasaki, H., Gonoi, W., Murakami, M., Katsura, M., Kunimatsu, A., Kawakubo, Y., Matsuzaki, H., Miyashita, Y., Kasai, K. and Yamasue, H.
    • Journal Title

      PloS One

      Volume: 7 Pages: e39561

    • DOI

      10.1371/journal.pone.0039561

    • Peer Reviewed
  • [Journal Article] To bet, or not to bet: that is the question of SEF spikes.2012

    • Author(s)
      Miyamoto, K., Hirabayashi, T. and Miyashita, Y.
    • Journal Title

      Neuron

      Volume: 75 Pages: 787-799

    • DOI

      10.1016/j.neuron.2012.07.012

    • Peer Reviewed
  • [Journal Article] A glass-coated tungsten microelectrode enclosing optical fibers for optogenetic exploration in primate deep brain structures.2012

    • Author(s)
      Tamura, K., Ohashi, Y., Tsubota, T., Takeuchi, D., Hirabayashi, T., Yaguchi, M., Matsuyama, M., Sekine, T. and Miyashita, Y.
    • Journal Title

      J. Neurosci. Methods

      Volume: 211 Pages: 49-57

    • DOI

      10.1016/j.jneumeth.2012.08.004

    • Peer Reviewed
  • [Journal Article] fMRI activity in the macaque cerebellum evoked by intracortical microstimulation of the primary somatosensory cortex: evidence for polysynaptic propagation.2012

    • Author(s)
      Matsui, T., Koyano, K.W., Tamura, K., Osada, T., Adachi, Y., Miyamoto, K., Chikazoe, J., Kamigaki, K. and Miyashita, Y.
    • Journal Title

      PLoS ONE

      Volume: 7 Pages: e47515

    • DOI

      10.1371/journal.pone.0047515

    • Peer Reviewed
  • [Presentation] Temporal neocortex shows antero-posterior functional dissociation during retrieval of remote memory.

    • Author(s)
      Watanabe, T., Kimura, H., Hirose, S., Wada, H., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y. and Konishi, S.
    • Organizer
      The 18th Annual Meeting of Organization of Huma Brain Mapping
    • Place of Presentation
      China National Convention Center Beijing, China
  • [Presentation] Cell-type-specific optogenetic inhibition of Purkinje cells reveals cerebellar control of blood pressure maintenance during postural alterations.

    • Author(s)
      Tsubota, T., Y. Ohashi, Tamura, K., Yaguchi, M., Matsuyama, M. Sekine, T. and Miyashita, Y.
    • Organizer
      The 35th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Nagoya Congress Center
  • [Presentation] Memory retrieval-related fMRI activity in the macaque posterior parietal cortex.

    • Author(s)
      Miyamoto, K., Osada, T., Adachi, Y., Matsui, T., Kimura, H. M. and Miyashita, Y.
    • Organizer
      The 35th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Nagoya Congress Center
  • [Presentation] Advances in experimental and theoretical approaches to understanding functional architecture of neural circuits: Granger causality analysis in monkey temporal cortex during perceptual and memory task.

    • Author(s)
      Hirabayashi, T., Takeuchi, D., Tamura, K. and Miyashita, Y.
    • Organizer
      The 35th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Nagoya Congress Center
  • [Presentation] Antero-posterior functional difference in the temporal neocortex during retrieval of remote memory.

    • Author(s)
      Watanabe, T., Kimura, H.M., Hirose, S., Wada, H., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y. and Konishi, S. 5. Watanabe, T., Kimura, H.M., Hirose, S., Wada, H., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y. and Konishi, S.
    • Organizer
      The 35th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Nagoya Congress Center
  • [Presentation] Cerebellar regulation of blood pressure during postural alterations revealed by Purkinje cell-specific optogenetic inhibition.

    • Author(s)
      Tsubota, T., Ohashi, Y., Tamura, K., Yaguchi, M., Matsuyama, M., Sekine, T. and Miyashita, Y.
    • Organizer
      The 42nd annual meeting of the Society for Neuroscience
    • Place of Presentation
      New Orleans Ernest N. Morial Convention Center, U.S.A.
  • [Presentation] Applying optogenetics to macaque deep brain structures: Development of a glass-coated tungsten optrode enclosing optical fibers.

    • Author(s)
      Tamura, K., Ohashi, Y., Tsubota, T., Takeuchi, D., Hirabayashi, T., Yaguchi,M.,Matsuyama, M., Sekine, T. and Miyashita, Y.
    • Organizer
      The 42nd annual meeting of the Society for Neuroscience
    • Place of Presentation
      New Orleans Ernest N. Morial Convention Center, U.S.A.
  • [Presentation] Convergence of category-specific information in the temporal neocortex during retrieval of remote memory.

    • Author(s)
      Watanabe, T., Kimura, H.M., Hirose, S., Wada, H., Katsura, M., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y. and Konishi, S.
    • Organizer
      The 42nd annual meeting of the Society for Neuroscience
    • Place of Presentation
      New Orleans Ernest N. Morial Convention Center, U.S.A.
  • [Presentation] Human association cortex is composed of functionally relevant micro-modules: a high-resolution fMRI study using resting-state functional connectivity.

    • Author(s)
      Hirose, S., Watanabe, T., Wada, H., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y. and Konishi, S.
    • Organizer
      The 90th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Tower Hall Funabori Tokyo
  • [Presentation] Differences in Anatomical Basis of Local vs Global Resting State Networks.

    • Author(s)
      Adachi, Y. and Miyashita, Y.
    • Organizer
      The 19th Annual Meeting of the Organization for Human Brain Mapping.
    • Place of Presentation
      Washington State Convention Center in Seattle, U.S.A.
  • [Remarks] Department of Physiology Miyashita Lab.

    • URL

      http://www.physiol.m.u-tokyo.ac.jp/index.html

URL: 

Published: 2015-05-28  

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