Neural substrate for regulation of sound-evoked emotional responses in mice

• Project/Area Number: 16K10218
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kumamoto University
• Principal Investigator: Takemoto Makoto 熊本大学, 大学院生命科学研究部(医), 講師 (20543408)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 弁別恐怖学習 / 二音弁別恐怖学習 / 島皮質 / BTBRマウス / 情動反応 / 精神神経科学 / 自閉症スペクトラム障害

Outline of Final Research Achievements

We aimed to reveal neural circuit mechanisms underlying regulation of sound-evoked emotional responses. We first established a paradigm of auditory discriminative fear conditioning in which mice learn to display either fear responses or safety responses, depending on the sound stimuli. This study provides a useful experimental system with a behavioral model for emotion regulation. We published a research article on this issue (Takemoto & Song, 2019, Lern Mem). Additionally, using this conditioning paradigm we found a fear generalization (i.e. an abnormal safety responses) in BTBR T+tf/J mice, a mouse model of autism spectrum disorders. We made a poster presentation on this finding in the 40th annual meeting of the Japan Neuroscience Society (2017).

Academic Significance and Societal Importance of the Research Achievements

本研究で構築した実験系は、音に対する恐怖反応と安心行動という相反する情動反応を観察できる系であり、この行動モデルを利用した情動制御の脳内メカニズムの研究の進展が期待できる。本実験系を用いた恐怖/安心の情動制御機構の研究は、自閉症スペクトラム障害や統合失調症、うつ病、心的外傷後ストレス障害などの神経精神疾患に共通して見られる不安障害の病態解明および治療法の開発に重要な示唆を与え得る。

Research Products

• [Journal Article] Cue-dependent safety and fear learning in a discriminative auditory fear conditioning paradigm in the mouse (2019)
  • Author(s): Takemoto Makoto、Song Wen-Jie
  • Journal Title: Learning & Memory Volume: 26 Issue: 8 Pages: 284-290
  • DOI: 10.1101/lm.049577.119
  • Peer Reviewed
• [Journal Article] A novel role of the antitumor agent tricyclodecan-9-yl-xanthogenate as an open channel blocker of KCNQ1/KCNE1 (2018)
  • Author(s): Wu, MK, Takemoto M, Luo H, Xu JJ, Lu MH, Kameyama M, Takumi T, Song WJ
  • Journal Title: Eur J Pharmacol Volume: 824 Pages: 99-107
  • DOI: 10.1016/j.ejphar.2018.02.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Organization of auditory areas in the superior temporal gyrus of marmoset monkeys revealed by real-time optical imaging (2017)
  • Author(s): Nishimura Masataka, Takemoto Makoto, Song Wen-Jie
  • Journal Title: Brain Structure and Function Volume: 223(4) Issue: 4 Pages: 1599-1614
  • DOI: 10.1007/s00429-017-1574-0
  • Peer Reviewed
• [Presentation] Anatomically-distinct neuronal subpopulations in layer 5 of insular cortex projecting to the extended amygdala in mice (2019)
  • Author(s): Makoto Takemoto, Wen-Jie Song
  • Organizer: Gordon Research Conference -Amygdala Function in Emotion, Cognition and Disease
  • Int'l Joint Research
• [Presentation] Anatomically-distinct neuronal subpopulations in layer 5 of insular cortex projecting to the extended amygdala in mice (2019)
  • Author(s): Makoto Takemoto, Wen-Jie Song
  • Organizer: Gordon Research Conference
  • Int'l Joint Research
• [Presentation] Anatomical organization and laminar distribution of subcortical projection neurons in the mouse insular cortex (2018)
  • Author(s): Makoto Takemoto, Wen-Jie Song
  • Organizer: 第41回日本神経科学学会
• [Presentation] Layer-specific subcortical circuits of the mouse insular cortex (2018)
  • Author(s): Makoto Takemoto, Wen-Jie Song
  • Organizer: 第5回生物音響学会
• [Presentation] Laminar distribution of anatomically distinct subpopulations of the mouse insular cortex neurons projecting to the central nucleus of the amygdala (2018)
  • Author(s): Makoto Takemoto, Wen-Jie Song
  • Organizer: 第41回日本神経科学大会
• [Presentation] Distinct projections from the primary and anterior auditory fields to motor and associative regions of the mouse neocortex (2017)
  • Author(s): Shiro Nakata, Makoto Takemoto, Wen-Jie Song
  • Organizer: 第4回生物音響学会
• [Presentation] The BTBR T+ tf/J mouse displays impaired safety and enhanced fear learning in an auditory discriminative fear conditioning paradigm (2017)
  • Author(s): Makoto Takemoto, Wen-Jie Song
  • Organizer: 第40回日本神経科学大会