Neuronal mechanisms of synaptic plasticity in the amygdala

• Project/Area Number: 25430015
• 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, 准教授 (00334277)
• Research Collaborator: KATO Fusao ; TAKAHASHI Yukari
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マウス / 情動 / 扁桃体 / 痛み / 神経回路 / 光遺伝学 / 慢性疼痛 / 記憶 / 可塑性 / 恐怖記憶 / 連合学習 / 無条件刺激 / 中心核 / 侵害受容 / 記憶・学習

Outline of Final Research Achievements

Pavlovian fear conditioning is accomplished by associating a conditioning stimulus (CS) and an unconditioned stimulus (US). While CS-US associations occur in the amygdala, the pathway mediating US signal has not been well identified. The lateral parabrachial nucleus (lPB) is well situated for providing US information to the central amygdala (CeA). Therefore, we manipulated the lPB-CeA pathway to examine its role in fear learning. First, transient inactivation of lPB during the conditioning with muscimol (MUS) significantly attenuated the freezing ratio on the retrieval test, suggesting that lPB activity is required for fear learning. Next, we injected channelrhodopsin2 expressing adeno-associated virus (AAV) into lPB. Selective stimulation of the lPB-CeA pathway in association with CS successfully created artificial fear memory without foot-shock. These results suggest that selective stimulation of the lPB-CeA pathway substitutes for the US to induce fear learning.

Research Products

• [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
• [Journal Article] The lateral parabrachial nucleus is actively involved in the acquisition of fear memory in mice (2015)
  • Author(s): Sato M, Ito M, Nagase M, Sugimura YK, Takahashi Y, Watabe AM, Kato F
  • Journal Title: Molecular Brain Volume: 8 Issue: 1 Pages: 22-22
  • DOI: 10.1186/s13041-015-0108-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA receptors in the neonatal mouse brain. (2014)
  • Author(s): Hamada, S., Ogawa, I., Yamasaki, M., Kiyama, Y., Kassai, H., Watabe, A.M., Nakao, K., Aiba, A., Watanabe, M., and Manabe, T.
  • Journal Title: European Journal of Neuroscience Volume: 40 Pages: 3136-46
  • Peer Reviewed / Open Access
• [Journal Article] On-Site Energy Supply at Synapses through Monocarboxylate Transporters Maintains Excitatory Synaptic Transmission. (2014)
  • Author(s): Nagase, M., Takahashi, Y., Watabe, A.M., Kubo, Y., and Kato, F.
  • Journal Title: J. Neurosci. Volume: 34 Pages: 2605-2617
  • Peer Reviewed
• [Journal Article] Impaired noradrenaline homeostasis in rats with painful diabetic neuropathy as a target of duloxetine analgesia. (2013)
  • Author(s): Kinoshita, J., Takahashi, Y., Watabe, A.M., Utsunomiya, K., and Kato, F.
  • Journal Title: Mol. Pain Volume: 9 Pages: 1-14
  • Peer Reviewed
• [Journal Article] Synaptic Potentiation in the Nociceptive Amygdala Following Fear Learning in Mice. (2013)
  • Author(s): Watabe AM, Ochiai T, Nagase M, Takahashi Y, Sato M, Kato F.
  • Journal Title: Mol. Brain Volume: 6 Pages: 1-14
  • Peer Reviewed
• [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
• [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: 横浜
  • Year and Date: 2016-07-20
• [Presentation] 侵害受容扁桃体における痛み情動回路の制御機構とその破綻 (2015)
  • Author(s): 渡部文子
  • Organizer: 包括脳冬のシンポジウム「新学術領域合同若手シンポジウム」
  • Place of Presentation: 東京
  • Year and Date: 2015-12-17
  • Invited
• [Presentation] 侵害受容扁桃体による情動記憶の制御. (2015)
  • Author(s): 渡部文子
  • Organizer: 平成27年度生理研研究会「情動の多次元的理解に基づく行動原理の探求」
  • Place of Presentation: 岡崎
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] Synaptic inputs from the lateral parabrachial nucleus to the central amygdala is actively involved in acquisition of fear memory. (2015)
  • Author(s): Watabe, A.M., Ito, M., Sato, M., Sugimura, Y.K., Takahashi, Y., Kato, F.
  • Organizer: Gordon research conference “Amygdala in Health and Disease”
  • Place of Presentation: Easton, 米国
  • Year and Date: 2015-08-02
  • Int'l Joint Research
• [Presentation] Optogenetic demonstration of direct input from the lateral parabrachial nucleus to the nociceptive amygdala. (2015)
  • Author(s): Sugimura YK, Takahashi Y, Watabe AM, Kato F.
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
  • Invited
• [Presentation] 侵害受容扁桃体による恐怖記憶制御の神経回路機構. (2014)
  • Author(s): 渡部文子
  • Organizer: 記憶回路研究会『個体内の記憶回路の同定とその機能解析による学習記憶制御基盤の統合的理解』
  • Place of Presentation: 岡崎
  • Year and Date: 2014-10-08 – 2014-10-09
  • Invited
• [Presentation] Two Distinct Types of Adrenoceptors Modurate Network Activity in The Central Nucleus of Amygdala. (2014)
  • Author(s): Yamamoto S, Takahashi Y, Watabe AM, Kato F.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] INSULIN ATTENUATES SYNAPTIC POTENTIATION IN THE NOCICEPTIVE AMYGDALA IN A RODENT MODEL OF PAINFUL DIABETIC NEUROPATHY. (2014)
  • Author(s): Takahashi Y, Ochiai T, Asato M, Watabe AM, Ohsawa M, Kamei J, Kato F.
  • Organizer: 9th FENS FORUM OF NEUROSCIENCE
  • Place of Presentation: ミラノ
  • Year and Date: 2014-07-05 – 2014-07-09
• [Presentation] Nociceptive Amygdala is Actively Involved in Fear Learning (2014)
  • Author(s): Ayako M. Watabe, Masaru Sato, and Fusao Kato
  • Organizer: 日本生理学会大会 シンポジウム
  • Place of Presentation: 鹿児島
• [Presentation] ラット顔面炎症性ホルマリン疼痛モデルにおける侵害受容扁桃体シナプス増強 (2014)
  • Author(s): 宮沢 祐太，高橋 由香里，渡部 文子, 加藤 総夫
  • Organizer: 日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] Involvement of Nociceptive Amygdala in Fear Learning (2013)
  • Author(s): Ayako M. Watabe
  • Organizer: Gordon Research Conference (Amygdala in Health and Disease) Hot Topics
  • Place of Presentation: 米国、ボストン
• [Presentation] Synaptic Potentiation in the Nociceptive Amygdala Following Fear Learning in Mice (2013)
  • Author(s): Ayako M. Watabe
  • Organizer: 日本神経科学学会大会 Neuro2013 シンポジウム
  • Place of Presentation: 京都
• [Presentation] Functional roles of monocarboxylate transporters in maintenance of neuronal functions in the cerebellum (2013)
  • Author(s): Masashi Nagase, Jun Noguchi, Ayako M. Watabe, Fusao Kato
  • Organizer: The 43rd annual meeting of the Society for Neuroscience
  • Place of Presentation: 米国、サンディエゴ
• [Presentation] Lateral parabrachial nucleus is involved in the acquisition of fear memory in mice. (2013)
  • Author(s): Masaru Sato, Ayako M. Watabe, Fusao Kato
  • Organizer: The 43rd annual meeting of the Society for Neuroscience
  • Place of Presentation: 米国、サンディエゴ