Molecular mechanisms of neural circuit development associated with fear and anxiety

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07263
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Niigata University
• Principal Investigator: Watanabe Keisuke 新潟大学, 医歯学系, 講師 (20446264)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 中隔核 / 恐怖行動 / Dpy19L1 / 細胞移動

Outline of Final Research Achievements

We previously observed abnormal innate fear responses and disorganization of the posterior septum (PS), which is related to fear and anxiety, in Dpy19L1 knockout (KO) mice. In this study, we found that central nervous system-specific Dpy19L1 conditional knockout mice showed abnormal innate fear responses, severe disorganization of the PS, and abnormal projections of the postcommissural fornix. Furthermore, we found that PS neurons utilize the postcommissural fornix as a scaffold for their migration during development. The cytoarchitecture of the PS was disorganized in cortex-specific Dpy19L1 knockout mice. Our results suggest that Dpy19L1 derived from the cerebral cortex regulate develpment of the PS in an indirect manner during embryonic stages.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

動物にとって恐怖や不安は極めて重要な情動の一つである。野生動物においては、天敵に対する恐怖は生存にとって必須であるし、ヒトにおいても過度な恐怖・不安は不安症などの障害に繋がり、社会的にも重要視されている。しかしながら、恐怖や不安の神経回路がどのような発生メカニズムで形成されるかはほとんどわかっていない。私達はDpy19L1 KOマウスが人を怖がらないという異常な行動を示すことに注目し、その発生異常の解析を進めてきた。本研究により、Dpy19L1がどのようなメカニズムで恐怖の神経回路発生を制御しているかがわかってきた。