Exploring physiological functions of hippocampal LTD using the PhotonSABER, a photo-activated synaptic plasticity control tool.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Keio University
• Principal Investigator: Itoh Masayuki 慶應義塾大学, 医学部(信濃町), 特任助教 (20442535)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 海馬 / シナプス可塑性 / LTD / 光遺伝学

Outline of Final Research Achievements

This research plan utilises a photo-activated LTD inhibition tool (PhotonSABER,　hereafter "PS") developed in the Yuzaki Laboratory at Keio University to elucidate the functions at the behavioural level that are causally related to long-term depression (LTD) in the hippocampus, which is involved in spatial memory and learning. We were able to generate the necessary tools for this research plan, knock-in mice expressing PS in excitatory neurons in the forebrain, and AAV vectors capable of whole-brain expression of PS by intravenous administration. But we could not be established the experimental condition that PS inhibit the LTD of hippocampal CA3-CA1 synapses, because we were unable to solve the problem of phototoxicity in the hippocampus.

Free Research Field

分子神経生物学

Academic Significance and Societal Importance of the Research Achievements

研究期間を通じて、光刺激による原因不明の毒性のためPhotonSABERの活性化に十分な強度の刺激を行えなえず、ex vivoのスライスレベルでの実験条件の確立が大きく停滞してしまい、その後のLTDの生理機能の解明に必要な行動実験に繋げることができなかった。しかしながら、ノックインマウスやAAVベクター等のツールの作製は完了しており、今後もこれらを利用し、他の脳部位、例えば扁桃体を標的として恐怖条件付けの行動実験をモデルとしてLTDと直接的な因果関係のある生理機能の解明に繋げたい。