ADHD model mice depending on thalamo-cortical circuits
| Project/Area Number |
15H04290
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Institute of Physical and Chemical Research |
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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)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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| 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 / ADHD / 視床 / 皮質 / トランスジェニックマウス / 多感覚統合 / 興奮性細胞 / 抑制性細胞 / 位相ロック / マウスモデル / 視床皮質回路 / 遺伝子変異マウス / 統合失調症 / 遺伝子治療 / 遺伝学 / 遺伝子 / 神経科学 / 動物 / 脳・神経 / 注意不全 / 遺伝子進化 |
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| 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.
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| 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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Report
(5 results)
Research Products
(25 results)
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[Journal Article] Schizophrenia-like phenotypes in mice with NMDA receptor ablation in intralaminar thalamic nucleus cells and gene therapy-based reversal in adults2017
Author(s)
Yasuda K, Hayashi Y, Yoshida T, Kashiwagi M, Nakagawa N, Michikawa T, Tanaka M, Ando R, Huang A, Hosoya T, McHugh TJ, Kuwahara M, Itohara S.
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Journal Title
Transl Psychiatry
Volume: 7
Issue: 2
Pages: e1047-e1047
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Developmental RacGAPa 2-chimaerin signaling is a determinant of the morphological features of dendritic spines in adulthood.2015
Author(s)
.Iwata, R., Matsukawa, H., Yasuda, K., Mizuno, H., Itohara, S., Iwasato, T.
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Journal Title
J. Nerurosci.
Volume: 35
Issue: 40
Pages: 13728-13744
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Involvement of cAMP-guanine nucleotide exchange factor II in hippocampal long-term depression and behavioral flexibility.2015
Author(s)
Lee K, Kobayashi Y, Seo H, Kwak JH, Masuda A, Lim CS, Lee HR, Kang SJ, Park P, Sim SE, Kogo N, Kawasaki H, Kaang BK, Itohara S.
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Journal Title
Molecular Brain
Volume: 8
Issue: 1
Pages: 38-38
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] A golden pair of synaptic adhesion molecules, netrin-G1 and netrin-G22016
Author(s)
Zhang Q, Goto H, Akiyoshi- Nishimura S, Prosselkov Pl, Sano C, Matsukawa H, Yaguchi K, Nakashib T, ItoharaS.
Organizer
ISN2016
Place of Presentation
Coimbra, Portugal
Year and Date
2016-06-01
Related Report
Int'l Joint Research
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