Role of "motivation" neurons in regulating autonomic nervous system function

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19709
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Tottori University
• Principal Investigator: Koba Satoshi 鳥取大学, 農学部, 教授 (40565743)
• Co-Investigator(Kenkyū-buntansha): 吉村 祐貴 鳥取大学, 医学部, 助教 (50771242)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: FosTRAP / 視床下部背側野 / 交感神経抑制 / 運動意欲

Outline of Final Research Achievements

We used newly generated FosTRAP rats via CRISPR/Cas9 system to investigate the distribution of excited hypothalamic neurons due to the motivation for running exercise as well as their roles in eliciting sympathetic outflow. Dorsal hypothalamus (DH) of rats that performed 2-h voluntary treadmill running with tamoxifen displayed a greater number of “FosTRAPed” neurons than that of control rats in which tamoxifen was administered during the resting period on the treadmill. Under urethane anesthesia, optogenetic stimulation of cell bodies of the running-exercise-FosTRAPed DH neurons decreased renal sympathetic nerve activity. Optogenetic stimulation of axons extending from the running-exercise-FosTRAPed DH neurons in the ventral medulla produced a pressor effect. These observations suggest both sympathoinhibitory and sympathoexcitatory DH neurons play roles in determining appropriate levels of sympathetic nerve activity during motivation-driven running exercise.

Free Research Field

自律神経生理学

Academic Significance and Societal Importance of the Research Achievements

抑うつ状態などの精神病態下で認められる自律神経機能不全は意欲低下の原因かつ結果である．しかし意欲と自律神経機能との連関メカニズムは研究自体がなかった．本研究では私たちが独自作出したラットFosTRAP法や光遺伝学などの遺伝子工学的技術を活用して，運動意欲の亢進に伴って興奮する視床下部神経による交感神経制御能を調査し，それらの役割を初めて明らかにした．本研究の知見は意欲と自律神経機能との因果性を担う脳実体に迫ったものであり，現代社会の病とも言える意欲の低下と関連した精神病態の新しい理解にもつながり，また未来医療の方策開発の基盤となる可能性も秘める．