Analysis of neural circuitry mechanism of the central amygdala in the control of feeding behavior

• Project/Area Number: 20K15929
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Nagoya University
• Principal Investigator: Ueda Shuhei 名古屋大学, 環境医学研究所, 助教 (10769037)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 扁桃体中心核 / 摂食行動 / 情動 / カルシウムイメージング

Outline of Research at the Start

食べるという行為は、私達が生命活動を行っていく上で必要なエネルギーや身体の恒常性維持に必要な栄養素を摂取するために必須の行動である。近年、過食や拒食をはじめとした摂食障害が増加傾向にあるが、根本的な原因や発症機構はわかっておらず、その病態の解明には摂食行動を駆動する神経回路機構の解読が必要である。本研究では、情動的摂食行動の異常が摂食障害の根底にあるという観点から、情動中枢の出力核として知られる扁桃体中心核に着目し、独自の行動動評価系と神経活動計測や神経回路操作を用いた解析を行う。

Outline of Final Research Achievements

It is thought that neural circuit of emotional regulation is involved in the control of feeding behavior, however its neural circuitry mechanism is still unclear. In this study, we focused on the central nucleus of the amygdala (CeA), which is the output nucleus of the emotional amygdala circuit, and recorded neuronal activity by using in vivo calcium imaging system about the three major cell-populations of the CeA. We analyzed neuronal activity responses in each cell population during feeding behavior, various tastant stimulations, and administration of gastrointestinal hormones, which are important factors of feeding behavior, and found that various feeding-related information are accumulated in the CeA and represented in a more complex way than previously thought.

Academic Significance and Societal Importance of the Research Achievements

近年増加傾向にある摂食障害の一因には、情動神経回路の機能異常による摂食行動調節機構の破綻があると考えられるが、その病態の理解は進んでいない。本研究の成果は、摂食行動を制御する情動システムとして扁桃体中心核が重要な役割を果たしていることを示唆しており、情動的摂食調節機構の全容解明の足がかりとなるものである。本研究による摂食行動調節の正常な神経回路機構の理解が、今後、摂食障害を呈する様々な精神疾患の病態理解につながると考えられる。

Research Products

• [Journal Article] Identification of ultra-rare disruptive variants in voltage-gated calcium channel-encoding genes in Japanese samples of schizophrenia and autism spectrum disorder (2022)
  • Author(s): Wang C, Horigane SI, Wakamori M, Ueda S, Kawabata T, Fujii H, Kushima I, Kimura H, Ishizuka K, Nakamura Y, Iwayama Y, Ikeda M, Iwata N, Okada T, Aleksic B, Mori D, Yoshida T, Bito H, Yoshikawa T, Takemoto-Kimura S, Ozaki N
  • Journal Title: Translational Psychiatry Volume: 12 Issue: 1 Pages: 84-84
  • DOI: 10.1038/s41398-022-01851-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinctive Regulation of Emotional Behaviors and Fear-Related Gene Expression Responses in Two Extended Amygdala Subnuclei With Similar Molecular Profiles (2021)
  • Author(s): Ueda S, Hosokawa M, Arikawa K, Takahashi K, Fujiwara M, Kakita M, Fukada T, Koyama H, Horigane SI, Itoi K, Kakeyama M, Matsunaga H, Takeyama H, Bito H, Takemoto-Kimura S.
  • Journal Title: Frontiers in Molecular Neuroscience Volume: 14 Pages: 741895-741895
  • DOI: 10.3389/fnmol.2021.741895
  • Peer Reviewed / Open Access
• [Journal Article] Remote control of neural function by X-ray-induced scintillation (2021)
  • Author(s): Matsubara Takanori、Yanagida Takayuki、Kawaguchi Noriaki、Nakano Takashi、Yoshimoto Junichiro、Sezaki Maiko、Takizawa Hitoshi、Tsunoda Satoshi P.、Horigane Shin-ichiro、Ueda Shuhei、Takemoto-Kimura Sayaka、Kandori Hideki、Yamanaka Akihiro、Yamashita Takayuki
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 4478-4478
  • DOI: 10.1038/s41467-021-24717-1
  • Peer Reviewed / Open Access
• [Journal Article] From population to neuron: exploring common mediators for metabolic problems and mental illnesses (2020)
  • Author(s): Takayanagi Yoichiro、Ishizuka Koko、Laursen Thomas M.、Yukitake Hiroshi、Yang Kun、Cascella Nicola G.、Ueda Shuhei、Sumitomo Akiko、Narita Zui、Horiuchi Yasue、Niwa Minae、Taguchi Akiko、White Morris F.、Eaton William W.、Mortensen Preben B.、Sakurai Takeshi、Sawa Akira
  • Journal Title: Molecular Psychiatry Volume: - Issue: 8 Pages: 3931-3942
  • DOI: 10.1038/s41380-020-00939-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development. (2020)
  • Author(s): Horigane SI, Ozawa Y, Zhang J, Todoroki H, Miao P, Haijima A, Yanagawa Y, Ueda S, Nakamura S, Kakeyama M, Takemoto-Kimura S.
  • Journal Title: FEBS Open Bio Volume: 10 Issue: 8 Pages: 1436-1446
  • DOI: 10.1002/2211-5463.12924
  • Peer Reviewed / Open Access
• [Presentation] PKCδ+ neurons in two central extended amygdala subnuclei differentially govern anxiety and fear (2021)
  • Author(s): Ueda S, Fukada T, Fujiwara M, Bito H, Takemoto-Kimura S.
  • Organizer: 第44回 日本神経科学大会
• [Presentation] Development of a novel mouse model of Timothy syndrome associated with autism spectrum disorder (2021)
  • Author(s): Hyodo F, Ozawa Y, Pan M, Ueda S, Abe M, Sakimura K, Horigane S, Takemoto-Kimura S.
  • Organizer: 第44回 日本神経科学大会