Molecular basis for memory decifits with abnormalities in synaptic morphology and circuit dynamics

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H02536
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: YAMAGATA Kanato 公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 研究員 (20263262)
• Co-Investigator(Kenkyū-buntansha): 田中 秀和 立命館大学, 生命科学部, 教授 (70273638) ; 平井 志伸 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (00625189)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 結節性硬化症 / 記憶痕跡細胞

Outline of Final Research Achievements

It is known that the shape of synapses changes during memory formation, but there is no evidence that synaptic abnormalities cause memory impairments. In this study, we focused on tuberous sclerosis (TSC) as a disease that causes memory impairments and compared memory trace cells involved in memory between wild-type and TSC model mice. As a result, we found that there were fewer active trace cells and less synaptic changes during memory recall in TSC model mice. Therefore, we administered a therapeutic candidate to the model mice, which resulted in an improvement in the activity of trace cells, synaptic morphology, and memory recovery. From these results, we suggest that synaptic morphological abnormalities can cause improper functioning of memory circuits and lead to memory impairments.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脳の高次機能、特に記憶の形成にシナプスの形態変化を伴うことは、自明の理となっている。しかし、記憶の異常を伴う病気や疾患モデルにおいて、シナプスの形態異常が記憶障害を起こすという直接の証拠は未だ示されていない。本研究では、記憶障害を示す疾患として結節性硬化症を取り上げ、そのモデルマウスを使用して、遺伝学的・薬理学的なシナプス形態・回路動態の改善が記憶の回復に寄与するかどうかを検証したい。