The effect of extracellular Calcium dynamics on synaptic transmission

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15562
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Keio University
• Principal Investigator: Arai Itaru 慶應義塾大学, 医学部(信濃町), 助教 (00754631)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 小脳 / 長期可塑性 / δ2型グルタミン酸受容体 / Dセリン / 細胞外Ca濃度

Outline of Final Research Achievements

Delta2 glutamate receptors (GluD2), which express in cerebellar parallel fiber - Purkinje cell synapses and induce long term depression by binding with D-serine (D-LTD), have Ca2+ binding sites at their ligand binding domain. In this study, I investigated how D-LTD is influenced by the extracellular Ca2+ concentration([Ca]o) dynamics during synaptic activities.
When [Ca]o was reduced during the LTD induction, D-LTD was facilitated. On the other hand, D-LTD was inhibited when [Ca]o was elevated during its induction. Moreover, D-LTD was always facilitated when the similar experiments were performed by using knock in mice that have mutant GluD2 whose Ca2+ binding ability was disrupted. These results indicate that D-serine - GluD2 signaling is regulated by the [Ca]o dynamics during synaptic activities.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

中枢神経系においてグルタミン酸によるシナプス伝達は神経活動依存的に様々な制御を受けて記憶・学習等の基盤となるが、その制御機構には未だ不明な点も多い。近年、グルタミン酸受容体の構造解析から細胞外領域にイオン結合部位が存在することが明らかになった。一方、シナプス近傍の細胞外イオン濃度は神経活動依存的に変化する。本研究は、小脳平行線維シナプスに局在するGluD2を用いて、細胞外イオン濃度の活動依存的変化がシナプス伝達を制御するという、これまで考えられてこなかった全く新しいシナプス制御機構の存在を示唆しており、得られた知見は他のグルタミン酸受容体を介したシナプス伝達の制御機構への応用も期待される。