The use of photoactivated adenylyl cyclase (PAC) in vitro and in vivo.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19440
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Koyama Ryuta 東京大学, 大学院薬学系研究科(薬学部), 准教授 (90431890)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: アストロサイト / サイクリックAMP / アデニル酸シクラーゼ / 記憶学習 / 光遺伝学

Outline of Final Research Achievements

To understand the role of astrocytic cyclic AMP (cAMP) in memory, we developed a transgenic mouse line in which astrocytes express photoactivated adenylyl cyclase (PAC), a protein which can be activated by blue light and rapidly changes its conformation to synthesize cAMP from ATP. In these mice, we optogenecically modulated the intracellular levels of cAMP in the hippocampal astrocytes and investigated the effect of a prolonged cAMP elevation in spatial memory. We found that the long-term cAMP elevation in astrocytes after training session facilitated the memory fading, while the short-term cAMP elevation enhanced memory formation. We also found that astrocytic cAMP facilitates synaptic plasticity through activating NMDA receptors, which may underlie both memory fading and enhanced memory formation. Thus, our results suggest that astrocytic cAMP signaling can modulate hippocampus-dependent learning and memory.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、記憶・学習を調節する新しい細胞生物学的メカニズムを明らかにした。すなわち、脳内細胞の大部分を占めるグリア細胞のアストロサイトが、細胞内cAMPシグナルの活性化を介して、記憶を双方向性（固定化と障害）に調節することが明らかになった。また、本研究では光遺伝学的手法を、一般的な神経細胞の活動調整ではなく、ではなくグリア細胞のセカンドメッセンジャーのシグナル調節にin vivoで用いるという学術的にも重要な挑戦を成功させた。