Characterization of neuronal networks in the amygdala underlying aversive information processing

• Project/Area Number: 16K07004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Watabe Ayako 東京慈恵会医科大学, 医学部, 教授 (00334277)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 扁桃体 / 情動 / マウス / 可塑性 / 神経ペプチド / 連合学習 / 痛み / 光遺伝学 / シナプス可塑性 / 経路特異性 / 回路 / シナプス / 可視化 / 神経科学 / 生理学 / 行動学

Outline of Final Research Achievements

The amygdala plays a key role in Pavlovian fear/threat conditioning which is accomplished by associating a conditioned stimuli (CS) and an unconditioned stimuli (US). While molecular mechanisms underlying CS-US association and plasticity in the CS pathway has been extensively studied, not much is known about the nature of US pathway(S) and their plasticity. Here we found that neuropeptide calcitonin gene-related peptide (CGRP) plays critical roles in formalin-induce behavioral plasticity in vivo as well as synaptic plasticity in the parabrachial-amygdaloid pathway in acute brain slices.

Academic Significance and Societal Importance of the Research Achievements

従来の研究では、連合学習におけるCS経路可塑性の分子メカニズムやその生理的意義が中心であったが、本研究成果によりUS経路の可塑性メカニズムの一端を明らかにすることができた。腕傍核から扁桃体への直接経路は慢性疼痛モデルや心的外傷後ストレス障害モデルにおいて可塑性異常が報告されており、本研究成果により、多様な疾患に伴う負情動制御破綻のメカニズム解明や将来的にはその治療法開発にも繋がる基礎的知見を得ることができた。

Research Products

• [Journal Article] Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes. (2020)
  • Author(s): Matsumura K, (33名中略）, Hashimoto R, (37名中35番目）,Hashimoto H, Nakazawa T.
  • Journal Title: Nat. Commun Volume: 11(1) Issue: 1 Pages: 859-859
  • DOI: 10.1038/s41467-020-14697-z
  • Peer Reviewed / Open Access
• [Journal Article] Parabrachial-to-amygdala control of aversive learning. (2019)
  • Author(s): Nagase, M., Mikami, K., and Watabe, A.M.
  • Journal Title: Current Opinion in Behavioral Sciences Volume: 26 Pages: 18-24
  • Peer Reviewed
• [Journal Article] Predominant synaptic potentiation and activation in the right central amygdala are independent of bilateral parabrachial activation in the hemilateral trigeminal inflammatory pain model of rats. (2018)
  • Author(s): Miyazawa,Y., Takahashi, Y., Watabe, A.M., Kato, F
  • Journal Title: Molecular pain Volume: 14 Pages: 1-21
  • Peer Reviewed
• [Journal Article] Essential role of endogenous calcitonin gene-related peptide in pain-associated plasticity in the central amygdala (2017)
  • Author(s): Shinohara Kei、Watabe Ayako M.、Nagase Masashi、Okutsu Yuya、Takahashi Yukari、Kurihara Hiroki、Kato Fusao
  • Journal Title: European Journal of Neuroscience Volume: 46 Issue: 6 Pages: 2149-2160
  • DOI: 10.1111/ejn.13662
  • Peer Reviewed / Open Access
• [Journal Article] Overlapping memory trace indispensable for linking, but not recalling, individual memories. (2017)
  • Author(s): Yokose, J., Okubo-Suzuki, R., Nomoto, M., Ohkawa, N., Nishizono, H., Suzuki, A., Matsuo, M., Tsujimura, S., Takahashi, Y., Nagase, M.,Watabe, A.M., Sasahara, M., Kato, F., Inokuchi, K.
  • Journal Title: Science Volume: 355 Issue: 6323 Pages: 398-403
  • DOI: 10.1126/science.aal2690
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cellular tagging as a neural network mechanism for behavioral tagging. (2016)
  • Author(s): Nomoto, M., Ohkawa, N., Nishizono, H., Yokose, J., Suzuki, A., Matuo, M., Tsujimura, S., Takahashi, Y., Nagase, M., Watabe, A.M., Kato, F., Inokuchi, K.
  • Journal Title: Nature Communications Volume: 7:12319 Issue: 1 Pages: 1-11
  • DOI: 10.1038/ncomms12319
  • Peer Reviewed / Open Access
• [Journal Article] Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala. (2016)
  • Author(s): Sugimura, YK., Takahashi, Y., Watabe, A.M., Kato, F.
  • Journal Title: Journal of neurophysiology Volume: ｘｘ Issue: 6 Pages: 2721-2739
  • DOI: 10.1152/jn.00946.2015
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced long-term potentiation in mature rats with a history of cryptogenic infantile spasms. (2016)
  • Author(s): Tsuji, M., Takahashi, Y., Watabe, A.M., Kato, F.
  • Journal Title: Epilepsia Volume: 57 Issue: 3 Pages: 495-505
  • DOI: 10.1111/epi.13315
  • Peer Reviewed / Open Access
• [Journal Article] SAD-B Kinase regulates presynaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory. (2016)
  • Author(s): Watabe, A.M., Nagase, M., Hagiwara, A., Hida, Y., Tsuji, M., Ochiai, T., Kato, F., Ohtsuka, T.
  • Journal Title: Journal of Neurochemistry Volume: 136: Issue: 1 Pages: 36-47
  • DOI: 10.1111/jnc.13379
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ASD-associated de novo POGZ mutations disrupt cortical development. (2019)
  • Author(s): Matsumura K, Seiriki K, Nagase M, Ayabe S, Yamada I, Furuse T, Yamamoto K, Kitagawa K, Baba M, Kasai A, Ago Y, Takano AH, Shintani N, Iguchi T, Sato M, Yamaguchi S, Tamura M, Wakana s, Yoshiki A, Watabe AM, Okano H, Takuma K, Hashimoto R, Hashimoto H, Nakazawa T.
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] ASD-related de novo POGZ mutations disrupt cortical neuronal differentiation. (2019)
  • Author(s): 松村憲佑, 勢力薫, 永瀬将志, 綾部信哉, 山田郁子, 古瀬民生, 山本果奈, 北川航平, 猪口徳一, 佐藤真, 山口瞬, 田村勝, 若菜茂晴, 吉木淳, 渡部文子, 岡野栄之, 田熊一敞, 橋本亮太, 橋本均, 中澤敬信.
  • Organizer: 第42回日本神経科学大会・第62回日本神経化学会大会
• [Presentation] Neuronal Circuits Underlying Regulation of Aversive Valence in Mice. (2019)
  • Author(s): 渡部文子
  • Organizer: FAOPS2019・第96回日本生理学会大会合同大会
  • Int'l Joint Research
• [Presentation] 味覚情動の形成と変容を支える神経回路基盤 (2018)
  • Author(s): 渡部文子
  • Organizer: 第11回香りと味に関する産学フォーラム
  • Invited
• [Presentation] 正と負の情動を担うシナプス制御機構とその破綻 (2018)
  • Author(s): 渡部文子
  • Organizer: 第2回和光-精神神経談話会
  • Invited
• [Presentation] Forming and reformatting aversive emotional memories “Neuronal circuits underlying emotional memories” (2018)
  • Author(s): 渡部文子
  • Organizer: 第41回日本神経科学大会
• [Presentation] 「痛み」から捉える情動記憶の神経回路メカニズム (2018)
  • Author(s): 渡部文子
  • Organizer: 東京大学理学部生物学科生物科学セミナー
• [Presentation] 情動行動を制御する扁桃体神経回路基盤 (2018)
  • Author(s): 渡部文子
  • Organizer: 第95回日本生理学会大会
  • Invited
• [Presentation] 情動の神経回路基盤 (2017)
  • Author(s): 渡部文子
  • Organizer: 第40回日本神経科学大会
  • Invited
• [Presentation] 痛み情動回路による恐怖記憶の制御 (2016)
  • Author(s): 渡部文子
  • 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] Neural circuits underlying flight-or- freeze behavior triggered by an environmental threat. (2016)
  • Author(s): M Ito, M Sat, M Nagase, Y K Sugimura, Y Takahashi, A M. Watabe and F Kato.
  • 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
• [Remarks] 東京慈恵会医科大学 総合医科学研究センター 臨床医学研究所 渡部研究室
  • URL: http://watabe-lab.jp/