Roles of amygdala glucocorticoid receptor in remote fear memory

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06902
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: University of Toyama
• Principal Investigator: Inoue Ran 富山大学, 学術研究部医学系, 助教 (70401817)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遠隔恐怖記憶 / 扁桃体 / グルココルチコイド受容体 / 記憶痕跡細胞

Outline of Final Research Achievements

A key feature of post-traumatic stress disorder (PTSD) is an intense and enduring memory for the trauma. However, the abnormalities in engram cells and circuits that underlie excessive remote fear memories has not been clarified. Lateral amygdala-selective glucocorticoid receptor knockout (LAGRKO) mice exhibit enhanced remote auditory fear memory. In this study, we found that in the auditory cortex (AC), the number of remote fear memory engram cells activated during fear conditioning was significantly smaller in LAGRKO mice than in control mice. By contrast, in the medial prefrontal cortex (mPFC), the number of remote fear memory engram cells activated during fear conditioning was significantly larger in LAGRKO mice than in control mice. These results suggest that abnormal organization of engrams in the AC and mPFC is associated with excessive remote fear memory after the trauma.

Free Research Field

神経科学、脳科学

Academic Significance and Societal Importance of the Research Achievements

遠隔恐怖記憶の異常な増強を示すLAGRKOマウスを用いた研究により、mPFCとACにおける記憶痕跡細胞の形成と変遷過程の異常が過剰な遠隔恐怖記憶の形成に関与することを明らかにした。また、LAからACへ強い投射があることを初めて明らかにし、LA-ACシナプスの情報伝達異常が過剰な遠隔恐怖記憶を形成する原因の一つである可能性を示唆した。本研究の成果は、PTSDの発症・悪化防止のための新規介入療法の提示に繋がる医学社会的波及効果があるだけでなく、恐怖記憶調節の基本原理の理解に貢献する学術的な波及効果があると考えられる。