Elucidation of the molecular and neural basis involved in motivation and behavioral reinforcement

2020 Fiscal Year Final Research Report

• Project Area: Creation and Promotion of the Will-Dynamics
• Project/Area Number: 16H06401
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: University of Tsukuba
• Principal Investigator: Sakurai Takeshi 筑波大学, 医学医療系, 教授 (60251055)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 意志力 / 覚醒 / オレキシン / ノルアドレナリン

Outline of Final Research Achievements

We have elucidated the role of the input-output system of orexin neurons in arousal, and how the arousal control system is involved in the function of the reward system, and how behavior can be altered through the reinforcement of emotional memory. We found that orexin regulates fear levels as well as arousal levels through NA neurons in the nucleus accumbens. Retrograde tracing of orexin and histamine neurons revealed a part of the arousal control system including the hypothalamus, brainstem and limbic system. We also clarified the role of GABAergic neurons in the striatum internus in inducing arousal. Furthermore, we showed that excitation of QRFP-positive neurons localized in the anterior ventral periventricular nucleus can induce a prolonged hypometabolic state.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

覚醒や気分は意志力に影響する重要な要素である。本研究では、オレキシンをはじめとする覚醒制御システムの解析を進め、覚醒系がモノアミン系を介して気分や情動に大きく影響を与えることも明らかにした。今後オレキシン受容体拮抗薬や作動薬が開発されていくことを考えると、これらの薬物が意志力に与える影響を考察する上で重要な知見を得られたと考えられる。