Analysis of plasticity of neurotransmission in the dentate granule cell synapses

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19316
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Doshisha University
• Principal Investigator: Hashimotodani Yuki 同志社大学, 研究開発推進機構, 准教授 (50401906)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 海馬 / シナプス可塑性 / CA3 / 苔状線維 / LTP

Outline of Final Research Achievements

Presynaptic long-term potentiation (LTP) is thought to play an important role in　learning and memory. However, the underlying mechanism remains elusive because of the difficulty of direct recording during LTP. Hippocam- pal mossy fiber synapses exhibit pronounced LTP of transmitter release after tetanic stimulation and have been used as a model of presynaptic LTP. Here, we induced LTP by optogenetic tools and applied direct presynaptic patch-clamp recordings. The action potential waveform and evoked presynaptic Ca2+ currents remained un- changed after LTP induction. Membrane capacitance measurements suggested higher release probability of synaptic vesicles without changing the number of release-ready vesicles after LTP induction. We propose that dynamic changes in the active zone components may be relevant for the increased fusion competence and synaptic vesicle replenishment during LTP.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

シナプス伝達効率が長時間に渡って増強する長期増強(LTP)は、記憶・学習の細胞レベルの基盤と考えられている。したがってLTPのメカニズムを細胞・分子レベルで明らかにすることは、記憶・学習の分子機構を理解するうえで極めて重要である。さらに認知症の治療やAI開発にも貢献する可能性がある。
したがってLTPの分子メカニズムを調べた本研究の成果は今後、ヒトでの応用を考慮した場合にも有用な知見を与えると期待される。