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2018 Fiscal Year Final Research Report

ADHD model mice depending on thalamo-cortical circuits

Research Project

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Project/Area Number 15H04290
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Itohara Shigeyoshi  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (60252524)

Project Period (FY) 2015-04-01 – 2019-03-31
Keywordsマウス / 注意 / 衝動性 / 精神疾患 / 遺伝子変異 / トランスジェニック / カルシウムセンサー
Outline of Final Research Achievements

To unravel molecular and circuit mechanisms underlying attention and impulse control, we analyzed a series of conditional mutants for NMDA receptor gene. The mutant mouse lime lacking NMDA receptors in neurons of intralaminar thalamic nucleus showed remarkable abnormalities in cognitive functions including attention, impulse control, and working memory, and REM sleep. We also provided evidence that NMDA receptors in hippocampal CA1 neurons have a role in determining subjective values of rewords, and thus effect on behaviors in delay discounting task. Using transgenic mouse lines that express calcium sensor proteins in a selective cell-type specific manner, we demonstrated that the medial and parietal association cortex has a crucial role in integrating information by multisensory stimulation.

Free Research Field

行動遺伝学

Academic Significance and Societal Importance of the Research Achievements

注意もしくは衝動性の制御に不全を持つ病態モデルマウスを樹立した。視床随板核のNMDA受容体機能不全が広範な脳機能に関わり、統合失調症の病理機構上、視床・皮質回路が重要な意義を持つことを明らかとした。病態理解に新たな視点をもたらしたもので、今後の治療戦略に資する。感覚刺激情報の統合の場を可視化しすることに成功し、情報統合による位相同期現象を発見した。精神疾患に随伴する神経回路機能異常の評価基準として有用である。

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Published: 2020-03-30  

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