The analysis of neural pathways in arousal maintenance and behavioral alteration under orexin

• Project/Area Number: 18K14846
• 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: University of Tsukuba
• Principal Investigator: Hasegawa Emi 筑波大学, 医学医療系, 助教 (40765955)
• Project Period (FY): 2018-04-01 – 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 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 睡眠 / ドーパミン / 扁桃体 / オレキシン / カタプレキシー / ファイバーフォトメトリー法 / in vivoレコーディングシステム / 睡眠・覚醒 / 報酬系 / ナルコレプシー / 光遺伝学的手法 / マルチユニット記録 / 覚醒・睡眠

Outline of Final Research Achievements

Since cataplexy has been shown to be induced by positive emotions, I focused on the dopamine nervous system which is highly associated with positive emotions. I observed a very unique pattern in dopamine release during cataplexy. I found that this dopamine pattern is an important factor in cataplexy. Furthermore, I found that NREM-to-REM transitions increase in dopamine in the amygdala during non-REM sleep. Positive emotions in individuals with cataplexy might lead to increases dopamine in the amygdala, mimicking the dynamics that trigger NREM-to-REM transitions.

Academic Significance and Societal Importance of the Research Achievements

扁桃体におけるドーパミン分泌量を制御することにより、レム睡眠量を自在に変化させることが可能になったことから、これを用いて、レム睡眠の役割を解明するとともに、睡眠・覚醒サイクルの生理学的意義の理解を進め、レム睡眠に関わる睡眠障害の発症メカニズムの解明や治療法の開発に役立つことが期待される。

Research Products

• [Journal Article] Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice (2022)
  • Author(s): Hasegawa Emi、Miyasaka Ai、Sakurai Katsuyasu、Cherasse Yoan、Li Yulong、Sakurai Takeshi
  • Journal Title: Science Volume: 375 Issue: 6584 Pages: 994-1000
  • DOI: 10.1126/science.abl6618
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice (2022)
  • Author(s): Emi Hasegawa, Ai Miyasaka, Katsuyasu Sakurai, Yoan Cherasse, Yulong Li, Takeshi Sakurai
  • Organizer: JST-CREST “Opt Bio” / WPI-IIIS Joint Symposium
  • Int'l Joint Research
• [Presentation] Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice (2022)
  • Author(s): Emi Hasegawa, Ai Miyasaka, Katsuyasu Sakurai, Yoan Cherasse, Yulong Li, Takeshi Sakurai,
  • Organizer: WPI-IIIS/Fudan University Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] レム睡眠関連脱力発作における扁桃体へのドーパミン放出の影響 (2019)
  • Author(s): 長谷川恵美、前島隆司、吉田隆行、柳沢正史、三枝理博、桜井武
  • Organizer: 第42回日本神経科学大会
• [Presentation] Neural circuits of cataplexy (2019)
  • Author(s): Emi Hasegawa, Ai Miyasaka, Takashi Maejima, Takayuki Yoshida, Katsuyasu Sakurai, Mitsuhiro Yoshioka, Masashi Yanagisawa, Michihiro Mieda, Takeshi Sakurai
  • Organizer: World sleep 2019
  • Int'l Joint Research / Invited
• [Presentation] Dopamine release into the amygdala might be involved in REM-related muscle atonia (2019)
  • Author(s): Emi Hasegawa, Ai Miyasaka, Takashi Maejima, Takayuki Yoshida, Katsuyasu Sakurai, Mitsuhiro Yoshioka, Masashi Yanagisawa, Michihiro Mieda, Takeshi Sakurai
  • Organizer: World sleep 2019
  • Int'l Joint Research
• [Presentation] Neural circuits of narcolepsy (2018)
  • Author(s): Emi Hasegawa, Takashi Maejima, Takayuki Yoshida, Olivia A. Masseck, Stefan Herlitze, Mitsuhiro Yoshioka, Masashi Yanagisawa, Michihiro Mieda, Takeshi Sakurai
  • Organizer: 第41回日本神経科学大会
• [Presentation] Neural circuits of narcolepsy (2018)
  • Author(s): Emi Hasegawa, Takashi Maejima, Takayuki Yoshida, Olivia A. Masseck, Stefan Herlitze, Mitsuhiro Yoshioka, Masashi Yanagisawa, Michihiro Mieda, Takeshi Sakurai
  • Organizer: The 11thFENS Forum of Neuroscience
  • Int'l Joint Research
• [Presentation] 扁桃体へのセロトニン神経入力はオレキシンを介して情動脱力発作の抑制する (2018)
  • Author(s): 長谷川恵美、前島隆司、吉田隆行、Olivia Masseck、Stefan Horlitze、吉岡充弘、柳沢正史、三枝理博、櫻井武
  • Organizer: 日本睡眠学会 第43回 定期学術集会
  • Invited
• [Presentation] ナルコレプシーの神経経路の探索 (2018)
  • Author(s): 長谷川恵美、前島隆司、三枝理博、櫻井武
  • Organizer: 日本睡眠学会 第43回 定期学術集会
  • Invited
• [Presentation] Search for neural circuits of narcolepsy-cataplexy (2018)
  • Author(s): Emi Hasegawa, Takashi Maejima, Takayuki Yoshida, Mitsuhiro Yoshioka, Masashi Yanagisawa, Michihiro Mieda, Takeshi Sakurai
  • Organizer: Society for Neuroscience
  • Int'l Joint Research