Brain-wide analysis of neuronal network dynamics underlying adaptive and maladaptive emotional responses

• Project/Area Number: 20H03556
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51020:Cognitive and brain science-related
• Research Institution: Osaka University
• Principal Investigator: Seiriki Kaoru 大阪大学, 大学院薬学研究科, 助教 (90802918)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: ストレス / 神経科学 / イメージング / 情動 / 全脳イメージング / 社会性行動 / アデノ随伴ウイルスベクター / 共焦点顕微鏡 / 薬理学 / 神経化学

Outline of Research at the Start

情動反応には大脳皮質や視床下部、青斑核を代表とする多数の脳領域が関与し、それらの活動および連関はストレス等の外的要因を受けて時間的・空間的に変化すると考えられる。本研究では、これまでに構築に携わってきた新規全脳イメージング技術FASTの改良と神経活動の多色標識マウスの構築を通して、脳全体における神経活動の時間・空間変化の解析法を確立し、ストレスによる情動の適応と変容の機序における相違点や分岐過程の機序の理解を目指す。

Outline of Final Research Achievements

Neuronal mechanisms underlying different stress responses caused by physiological and pathological stress remain unclear. Using three-dimensional imaging analysis of stress-induced neuronal activity across the entire brain, we identified the neuronal populations and their circuit structures responsible for stress-induced emotional alterations depending on the stress states. Moreover, using our brain-wide analysis of axonal projection, we revealed the circuit structure of neuronal populations responsive to an antipsychotic drug.

Academic Significance and Societal Importance of the Research Achievements

ストレスによる情動変容の神経基盤を、脳全体の時間・空間的な神経活動変化に基づいて明らかにした本研究は、将来的にヒト疾患との関連性などを検証していくことによって、ストレス関連疾患の病態理解や、治療戦略の確立に貢献できる可能性が考えられる。また、本研究を通して確立してきた神経活動変化や神経回路構造の解析方法は、他の病態モデル動物や薬物の治療効果における神経回路レベルのメカニズムを理解するための研究への貢献が期待できる。

Research Products

• [Journal Article] Clozapine Induces Neuronal Activation in the Medial Prefrontal Cortex in a Projection Target-Biased Manner (2024)
  • Author(s): Yumi Hirato, Kaoru Seiriki, Leo Kojima, Shohei Yamada, Hiroki Rokujo, Tomoya Takemoto, Takanobu Nakazawa, Atsushi Kasai, Hitoshi Hashimoto
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 47 Issue: 2 Pages: 478-485
  • DOI: 10.1248/bpb.b23-00898
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2024-02-22
  • Peer Reviewed / Open Access
• [Journal Article] Oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome (2022)
  • Author(s): Takemoto Tomoya、Baba Masayuki、Yokoyama Kazumasa、Kitagawa Kohei、Nagayasu Kazuki、Ago Yukio、Seiriki Kaoru、Hayata-Takano Atsuko、Kasai Atsushi、Mori Daisuke、Ozaki Norio、Takuma Kazuhiro、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
  • Journal Title: Molecular Brain Volume: 15 Issue: 1 Pages: 26-26
  • DOI: 10.1186/s13041-022-00915-w
  • Peer Reviewed / Open Access
• [Journal Article] Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses. (2022)
  • Author(s): Niu M, Kasai A, Tanuma M, Seiriki K, Igarashi H, Kuwaki T, Nagayasu K, Miyaji K, Ueno H, Tanabe W, Seo K, Yokoyama R, Ohkubo J, Ago Y, Hayashida M, Inoue KI, Takada M, Yamaguchi S, Nakazawa T, Kaneko S, Okuno H, Yamanaka A, Hashimoto H.
  • Journal Title: Science Advances Volume: 8 Issue: 11
  • DOI: 10.1126/sciadv.abi6375
  • Peer Reviewed / Open Access
• [Journal Article] Multiple alterations in glutamatergic transmission and dopamine D2 receptor splicing in induced pluripotent stem cell-derived neurons from patients with familial schizophrenia (2021)
  • Author(s): Yamamoto Kana、Kuriu Toshihiko、Takuma Kazuhiro、Ono Fumihito、Matsumoto Naomichi、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
  • Journal Title: Translational Psychiatry Volume: 11 Issue: 1 Pages: 548-548
  • DOI: 10.1038/s41398-021-01676-1
  • Peer Reviewed / Open Access
• [Journal Article] Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder (2021)
  • Author(s): Kitagawa Kohei、Matsumura Kensuke、Baba Masayuki、Kondo Momoka、Takemoto Tomoya、Nagayasu Kazuki、Ago Yukio、Seiriki Kaoru、Hayata-Takano Atsuko、Kasai Atsushi、Takuma Kazuhiro、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
  • Journal Title: Molecular Brain Volume: 14 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s13041-021-00769-8
  • Peer Reviewed / Open Access
• [Presentation] Whole-brain mapping of locus coeruleus noradrenergic projections in mice (2023)
  • Author(s): Kaoru Seiriki, Atsushi Kasai, Hitoshi Hashimoto
  • Organizer: 第66回日本神経化学会大会
• [Presentation] Development of an AAV vector for noradrenergic neuron-specific gene expression and application to mesoscale analysis of noradrenergic wiring diagrams in mice. (2023)
  • Author(s): Kaoru Seiriki, Shunsuke Maeda, Leo Kojima, Atsushi Kasai, Hitoshi Hashimoto
  • Organizer: Neuroscience 2023
  • Int'l Joint Research
• [Presentation] Identification of the medial prefrontal circuit responsive to the atypical antipsychotic drug clozapine (2023)
  • Author(s): Yumi Hirato, Kaoru Seiriki, Shohei Yamada, Leo Kojima, Atsushi Kasai, Takanobu Nakazawa, Hitoshi Hashimoto
  • Organizer: 第97回日本薬理学会年会
• [Presentation] Development of a noradrenergic neuron-selective AAV vector and brain-wide axonal mapping of social stress-responsive noradrenergic neurons (2022)
  • Author(s): Kaoru Seiriki, Shunsuke Maeda, Yuzuka Fujimoto, Shohei Yamada, Yumi Hirato, Atsushi Kasai, Hitoshi Hashimoto
  • Organizer: Neuro2022(第45回日本神経科学大会・第65回日本神経化学会大会・第32回日本神経回路学会大会)
• [Presentation] Social defeat stress induces activation of PACAP-expressing neurons in thermoregulatory systems (2022)
  • Author(s): Yuzuka Fujimoto, Kaoru Seiriki, Shunsuke Maeda, Taiyou Baba, Atsuko Hayata-Takano, Atsushi Kasai, Hitoshi Hashimoto
  • Organizer: The 15th International Symposium on VIP, PACAP and Related Peptides The 1st International Society for BioactivePeptides Meeting
  • Int'l Joint Research
• [Presentation] Development of a noradrenergic neuron-selective AAV vector and its application to the brain-wide axonal mapping (2022)
  • Author(s): Kaoru Seiriki, Shohei Yamada, Shunsuke Maeda, Yuzuka Fujimoto, Atsushi Kasai, Hitoshi Hashimoto
  • Organizer: 第９５回日本薬理学会年会
• [Presentation] ストレスの強度に応じた社会性の低下に関与する神経基盤のイメージング解析 (2021)
  • Author(s): 前田駿介、藤本柚香、勢力薫、山田翔平、平戸祐充、馬場太陽、児島励央、疋田貴俊、笠井淳司、橋本均
  • Organizer: 第140回薬理学会近畿部会