Identification and unraveling of the micro-endophenotypes at the molecular, cellular and circuit levels using model mice of psychiatric disorders associated with environmental factors

2016 Fiscal Year Final Research Report

• Project Area: Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels.
• Project/Area Number: 24116008
• 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: Tokyo University of Agriculture
• Principal Investigator: Kida Satoshi 東京農業大学, 応用生物科学部, 教授 (80301547)
• Co-Investigator(Kenkyū-buntansha): McHugh Thomas 国立研究開発法人理化学研究所, その他部局等, その他 (50553731)
• Co-Investigator(Renkei-kenkyūsha): KIM Yoshiharu 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 成人精神保健研究部, 部長 (60225117) ; KOBAYASHI Kazuto 福島県立医科大学, 医学部, 教授 (90211903)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: 神経科学 / 精神疾患 / 脳・神経 / PTSD / 恐怖記憶 / 記憶再固定化 / 記憶消去 / 記憶想起

Outline of Final Research Achievements

We tried to identify and understand the micro-endopenotypes of psychiatric disorders associated with environmental factors such as PTSD. To do this, we developed mouse model of PTSD that showed enhancement of fear after traumatic memory retrieval. This model showed that fear is enhanced through the activation of gene expression and protein degradation in the hippocampus-amygdala-mPFC circuits after fear memory retrieval. These findings suggest that over-activation of these circuits after fear memory retrieval is a candidate of micro-endopenotypes that causes PTSD. Furthermore, we found that remote fear memory returns to a hippocampus dependent state after long time recall. Using this phenomenon, we showed that following prolonged fear memory retrieval, hippocampal neurogenesis enhancers promote forgetting of remote contextual fear memory. Therefore, we proposed that forgetting of traumatic memory contributes to the development of PTSD treatment.

Free Research Field

神経科学