Analysis of cannabinoids-mediated modulation of synaptic transmission by direct patch-clamp recordings

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15189
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kyoto University
• Principal Investigator: Inoshita Takuma 京都大学, 理学研究科, 助教 (00880337)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: シナプス / 伝達物質放出 / カンナビノイド / パッチクランプ / プルキンエ細胞 / シナプス修飾 / CB2 / GPR55

Outline of Final Research Achievements

Neuronal communication is the basis of brain function. Synaptic transmission is negatively regulated by cannabinoids at various synapses in the central nervous system. Modulation of transmission by cannabinoids, extracted from cannabis and known for their psychoactive effects, have been extensively studied. However, the mechanisms of cannabinoids-mediated suppression of synaptic transmission remains obscure. In this study, paired patch-clamp recordings were performed from a presynaptic terminal of a Purkinje cell and its postsynaptic cell. We identified two suppressive actions of distinct cannabinoid receptors on presynaptic transmitter release: CB2 reduces presynaptic Ca2+ influx, while GPR55, a novel type of cannabinoid receptor, decreases fusion-competent vesicles susceptible to action potentials.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究は新しく同定されたGPR55について、よく分かっていなかったシナプス修飾メカニズムを詳細に示した。そのメカニズムは従来の理解とは異なる新規性の高いシナプス前部の機能調節である。カンナビノイドは向精神作用や鎮痛作用があるため社会的注目度が高く、本知見はそれらの理解深化に寄与し得る。特に、カンナビジオールというカンナビノイドの一種はてんかん治療や鎮痛薬として期待されており、GPR55にも結合するため、本研究成果が社会的・医学的応用に幅広くつながる可能性もある。