Constructive understanding of PTSD by synaptic manipulation

2022 Fiscal Year Final Research Report

• Project Area: Constructive understanding of multi-scale dynamism of neuropsychiatric disorders
• Project/Area Number: 18H05434
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: Hayashi Yasunori 京都大学, 医学研究科, 教授 (90466037)
• Co-Investigator(Kenkyū-buntansha): 喜田 聡 東京大学, 大学院農学生命科学研究科(農学部), 教授 (80301547)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: 心的外傷後ストレス障害 / 恐怖記憶 / シナプス可塑性 / cAMP / 海馬 / 記憶固定化と再固定化 / 光遺伝学 / 時計遺伝子

Outline of Final Research Achievements

We have established a system to inactivate cofilin, which enters the synapse upon LTP, using a photosensitizing protein. We found that we can erase LTP which was once established,. Next, we showed that fear memory can be eliminated in animals. Using transcriptome analysis, we compared mRNA expression in the peripheral blood of patients with PTSD re-experiencing symptoms with mRNA expression in the hippocampus of mice after fear memory recall, and identified a group of genes that were commonly down-regulated in both groups. Since these genes decrease cAMP levels, we hypothesized that the decreased expression of these genes leads to activation of the cAMP signaling pathway. We proceeded to analyze the mechanism of fear memory by optogenetically manipulating the activity of the fear memory engram in the hippocampus during fear memory recall.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

恐怖記憶は危険を避け、生存を保証する重要な脳の機能であるが、その異常な発言が心的外傷後ストレス障害で認められる。また薬物依存で観察される薬物非常に強い渇望も異常な記憶の一種と考えることができる。本研究で、記憶のメカニズムが理解され、さらにそれを操作することができるようになったのは将来的にこれらの疾患の治療戦略にも繋がり、意義が大きいと考えられる。