論文

査読有り
2017年3月

Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling

TRANSLATIONAL PSYCHIATRY
  • M. Toritsuka
  • ,
  • S. Kimoto
  • ,
  • K. Muraki
  • ,
  • M. Kitagawa
  • ,
  • T. Kishimoto
  • ,
  • A. Sawa
  • ,
  • K. Tanigaki

7
3
開始ページ
e1049
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/tp.2017.21
出版者・発行元
NATURE PUBLISHING GROUP

Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist. RBP-J deficiency drastically reduced dopamine release in the striatum and caused a subtle decrease in the number of dopaminergic neurons. Lentivirus-mediated gene transfer experiments showed that RBP-J deficiency in the striatum was sufficient for these deficits. These findings demonstrated that Notch/RBP-J signaling regulates dopamine responsiveness in the striatum, which may explain the mechanism whereby Notch/RBP-J signaling affects an individual's susceptibility to neuropsychiatric disease.

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1038/tp.2017.21
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28267151
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000397228200001&DestApp=WOS_CPL