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2015 年度 実績報告書

Dopaminergic regulation of fear extinction learning

研究課題

研究課題/領域番号 15H04264
研究機関国立研究開発法人理化学研究所

研究代表者

JOHANSEN JOSHUA  国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (80625351)

研究期間 (年度) 2015-04-01 – 2018-03-31
キーワードdopamine / fear / extinction learning
研究実績の概要

In Heisei 27 we made a great deal of progress. we set out to examine how fear memories can be reduced when they are no longer appropriate, a process called extinction learning. We first examined whether dopamine neurons in the ventral tegmental area (VTA), whic are important for reward, detect when fear memories are no longer appropriate to signal extinction learning. In the last year we found that activity in dopamine neurons when aversive outcomes are expected yet don't occur is required to extinguish fear memories. To do this we expressed optogenetic proteins in a genetically modified rat to inhibit dopamine neurons in a temporally and cell type specific manner. We then examine the effects of this manipulation on intracellular signaling in areas that store extinction memories, the amygdala and medial prefrontal cortex. We found that in addition to blocking extinction learning, inhibiting dopamine neurons during unexpected omission of aversive outcomes also blocked the phosphorylation of MAP kinase in amygdala and mPFC.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

everything is going smoothly

今後の研究の推進方策

Separate populations of VTA dopamine neurons project to the amygdala, mPFC and nucleus accumbens. In the next fiscal year we will examine the contribution of these specific cell VTA-dopamine cell populations to extinction learning. specifically we will use a genetically modified TH-cre rat to express an inhibitory opsin in dopamine neurons and in their nerve terminals in the amygdala, mPfC and accumbens. We will then inhibit nerve terminal release in these regions and examine the effects of these manipulations on extinction learning and memory.

  • 研究成果

    (6件)

すべて 2016 2015

すべて 雑誌論文 (3件) (うち国際共著 3件、 査読あり 3件、 謝辞記載あり 2件、 オープンアクセス 1件) 学会発表 (3件) (うち国際学会 1件、 招待講演 3件)

  • [雑誌論文] Evaluation of ambiguous associations in the amygdala by learning the structure of the environment.2016

    • 著者名/発表者名
      Madarasz, T.J., Diaz-Mataix, L., Akhand, O., Ycu, E.A., LeDoux, J.E., Johansen, J.P.
    • 雑誌名

      Nature Neuroscience

      巻: In press ページ: In press

    • DOI

      doi:10.1038/nn.4308

    • 査読あり / 国際共著 / 謝辞記載あり
  • [雑誌論文] Alterations in the rostral ventromedial medulla after the selective ablation of mu-opioid receptor expressing neurons.2016

    • 著者名/発表者名
      Harasawa, I., Johansen, J.P., Fields, H.L., Porreca, F., Meng, I.D.
    • 雑誌名

      Pain

      巻: 157(1) ページ: 166-173

    • DOI

      10.1097/j.pain.0000000000000344

    • 査読あり / 国際共著
  • [雑誌論文] Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory.2015

    • 著者名/発表者名
      Uematsu, A., Tan, B.Z., Johansen, J.P.
    • 雑誌名

      Learning & Memory

      巻: 22 ページ: 444-451

    • DOI

      10.1101/lm.037283.114

    • 査読あり / オープンアクセス / 国際共著 / 謝辞記載あり
  • [学会発表] Neural circuit mechanisms for triggering and reversing aversive memories2016

    • 著者名/発表者名
      Joshua Johansen
    • 学会等名
      Neural mechanisms of decision making: achievements and new directions
    • 発表場所
      CiNet Bldg Conference room, Osaka, Japan
    • 年月日
      2016-02-03 – 2016-02-03
    • 招待講演
  • [学会発表] A feedback neural circuit for calibrating memory strength2015

    • 著者名/発表者名
      Joshua Johansen
    • 学会等名
      International Symposium on Optogenetics (Tokyo, Japan)
    • 発表場所
      Akio Suzuki Memorial Hall, Tokyo, Japan
    • 年月日
      2015-12-05 – 2015-12-05
    • 招待講演
  • [学会発表] Functional and anatomical specificity in locus coeruleus noradrenaline neurons2015

    • 著者名/発表者名
      Joshua Johansen
    • 学会等名
      Gordon Conference: Amygdala in health and disease
    • 発表場所
      Easton, USA
    • 年月日
      2015-08-04 – 2015-08-04
    • 国際学会 / 招待講演

URL: 

公開日: 2017-01-06  

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